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1.
Metab Syndr Relat Disord ; 21(1): 41-47, 2023 02.
Article in English | MEDLINE | ID: mdl-36318507

ABSTRACT

Background: Nonalcoholic fatty liver disease (NAFLD) is generated by the interaction between environmental and genetic factors, and the presence of metabolic alterations. Since Taq1B cholesteryl ester transfer protein (CETP) polymorphism is associated with abnormal serum lipid values, it could be related to NAFLD. The aim of this study was to determine the role of the Taq1B CETP polymorphism with serum lipids, anthropometric variables, and the extent of steatosis in Mexican-mestizo women with gallstone disease (GD). Methods: Sixty-two women were enrolled in this cross-sectional study. Serum lipids were determined by dry chemistry. The Taq1B CETP polymorphism was determined by allelic discrimination. CETP serum levels were measured by enzyme-linked immunosorbent assay, and the extent of steatosis with a biopsy staining with Oil-Red-O. Results: Subjects with the B1B2/B2B2 genotype had higher percentage of degree of steatosis than those with B1B1 (11.95% vs. 2.19%, P = 0.008). The B1B2/B2B2 genotype (odds ratio [OR] 3.90 [confidence interval {CI} 95% 1.891-8.536], P = 0.04) and an elevated low-density lipoproteins (LDL)-cholesterol (OR 3.54 [CI 95% 1.042-2.058, P = 0.039) significantly increase the risk for NAFLD. Conclusions: This study provides evidence that the B1B2/B2B2 genotype of CETP and the elevated LDL-cholesterol serum levels increase the risk of NAFLD in women with GD.


Subject(s)
Cholelithiasis , Non-alcoholic Fatty Liver Disease , Humans , Female , Cholesterol Ester Transfer Proteins/genetics , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Cross-Sectional Studies , Genotype , Cholesterol, HDL , Lipoproteins, LDL
2.
Nutrients ; 14(22)2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36432414

ABSTRACT

The carbohydrate response element binding protein (ChREBP) is a key transcription factor to understand the gene−diet−nutrient relationship that leads to metabolic diseases. We aimed to analyze the association between the rs17145750 and rs3812316 SNVs (single nucleotide variants) of the MLXIPL gene with dietary, anthropometric, and biochemical variables in Mexican Mestizo subjects. This is a cross-sectional study of 587 individuals. Genotyping was performed by allelic discrimination. In addition, liver and adipose tissue biopsies were obtained from a subgroup of 24 subjects to analyze the expression of the MLXIPL gene. An in silico test of the protein stability and allelic imbalance showed that rs17145750 and rs3812316 showed a high rate of joint heritability in a highly conserved area. The G allele of rs3812316 was associated with lower triglyceride levels (OR = −0.070 ± 0.027, p < 0.011, 95% CI = −0.124 to −0.016), the production of an unstable protein (ΔΔG −0.83 kcal/mol), and probably lower tissue mRNA levels. In addition, we found independent factors that also influence triglyceride levels, such as insulin resistance, HDL-c, and dietary protein intake in women. Our data showed that the association of rs3812316 on triglycerides was only observed in patients with an inadequate alpha-linolenic acid intake (1.97 ± 0.03 vs. 2.11 ± 0.01 log mg/dL, p < 0.001).


Subject(s)
Dietary Proteins , alpha-Linolenic Acid , Humans , Female , Triglycerides/genetics , Cross-Sectional Studies , Polymorphism, Single Nucleotide , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Nucleotides
3.
Exp Clin Endocrinol Diabetes ; 128(11): 715-722, 2020 Nov.
Article in English | MEDLINE | ID: mdl-30754064

ABSTRACT

The expansion of adipose tissue is regulated by insulin and leptin through sterol regulatory element-binding protein-1c (SREBP-1c), up-regulating lipogenesis in tissues by Stearoylcoenzyme A desaturase 1 (SCD1) enzyme, while adipose triglyceride lipase (ATGL) enzyme is key in lipolysis. The research objective was to evaluate the expression of Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1), SCD1, Patatin Like Phospholipase Domain Containing 2 (PNPLA2), and leptin (LEP) genes in hepatic-adipose tissue, and related them with the increment and distribution of fat depots of individuals without insulin resistance. Thirty-eight subjects undergoing elective cholecystectomy with liver and adipose tissue biopsies (subcutaneous-omental) are included. Tissue gene expression was assessed by qPCR and biochemical parameters determined. Individuals are classified according to the body mass index, classified as lean (control group, n=12), overweight (n=11) and obesity (n=15). Abdominal adiposity was determined by anthropometric and histopathological study of the liver. Increased SCD1 expression in omental adipose tissue (p=0.005) and PNPLA2 in liver (p=0.01) were found in the obesity group. PNPLA2 decreased expression in subcutaneous adipose tissue was significant in individuals with abdominal adiposity (p=0.017). Anthropometric parameters positively correlated with liver PNPLA2 and the expression of liver PNPLA2 with serum leptin. SCD1 increased levels may represent lipid storage activity in omental adipose tissue. Liver PNPLA2 increased expression could function as a primary compensatory event of visceral fat deposits associated to the leptin hormone related to the increase of adipose tissue.


Subject(s)
Leptin/metabolism , Lipase/metabolism , Liver/metabolism , Overweight/metabolism , Stearoyl-CoA Desaturase/metabolism , Subcutaneous Fat/metabolism , Adult , Body Mass Index , Female , Gene Expression/physiology , Humans , Male , Obesity/metabolism
4.
Iran J Basic Med Sci ; 22(6): 623-630, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31231489

ABSTRACT

OBJECTIVES: The present study aimed to evaluate the receptor of advanced glycation end-products (RAGE), NF-kB, NRF2 gene expression, and RAGE cell distribution in peripheral blood mononuclear cells (PBMC) in subjects with obesity and IR compared with healthy subjects. MATERIALS AND METHODS: The mRNA expression levels of RAGE, NF-kB, NRF2, and GAPDH were determined in PBMC by qPCR in 20 obese (OB), 17 obese with insulin resistance (OB-IR), and 20 healthy subjects (HS), matched by age and sex. RAGE protein expression and its localization were determined by Western Blot and immunocytochemistry (ICC) analysis, total soluble RAGE (sRAGE) and MCP-1 plasma levels by ELISA. RESULTS: RAGE, NF-kB, and NRF2 genes mRNA expression in PBMCs did not show variation between groups. RAGE protein was lower in OB and OB-IR groups; RAGE was located predominantly on the cell-surface in the OB-IR group compared to the HS group (22% vs 9.5%, P<0.001). OB-IR group showed lower sRAGE plasma levels, and correlated negatively with HOMA-IR, ALT parameters (r= -0.374, r= -0.429, respectively), and positively with NFE2L2 mRNA (r= 0.540) P<0.05. CONCLUSION: In this study, OB-IR subjects did not reflect significant differences in gene expression; however, correlations detected between sRAGE, biochemical parameters, and NRF2, besides the predominant RAGE distribution on the cell membrane in PBMC could be evidence of the early phase of the inflammatory cascade and the subsequent damage in specific tissues in subjects with OB-IR.

5.
Scand J Clin Lab Invest ; 79(3): 218-224, 2019 May.
Article in English | MEDLINE | ID: mdl-30813849

ABSTRACT

Most quantitative real-time PCR (qPCR) detection methods use two types of chemistries to measure the expression levels of ChREBP isoforms, hydrolysis probes for ChREBPα and SYBR Green for ChREBPß. Hydrolysis probes are not available to determine the ChREBPß isoform. The aim of this study was to develop a qPCR assay based only on hydrolysis probes for both ChREBP isoforms. Liver and adipose tissue biopsies from patients undergoing elective cholecystectomy surgery were used to perform qPCR. To validate this assay, the results were compared with sequencing and High Resolution Melting (HRM) PCR assays. Direct sequencing was used to determine the sequence showing site where ChREBPß presents its specific splicing (1 b exon/2 exon) in order to design the primers and the probe. We developed a qPCR assay to determine the ChREBP isoforms expression based on hydrolysis probes. It assays showed good efficiency (95.50%, on average), high reproducibility, and a strong linear correlation (R2 ≥ 0.99) for tissues tested. HRM analysis confirmed the specificity of the primers and the result of this assay matched (100%) with the outcomes obtained by sequencing and qPCR. Also, we obtained the ChREBPß sequence showing exon 1b spliced to exon 2, bypassing exon 1a, and retaining the remainder of the ChREBPα exons. Based on the use of hydrolysis probes, our method can efficiently identify the expression of both ChREBP isoforms. Thus, the comparability of the qPCR results using a single chemistry (hydrolysis probes) to discriminate between both ChREBP isoforms was possible.


Subject(s)
Adipose Tissue/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Liver/metabolism , Real-Time Polymerase Chain Reaction/methods , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Humans , Omentum/metabolism , Protein Isoforms/metabolism , Subcutaneous Tissue/metabolism
6.
Med. clín (Ed. impr.) ; 150(7): 251-256, abr. 2018. tab
Article in Spanish | IBECS | ID: ibc-173424

ABSTRACT

Introducción y objetivo: Cambios moleculares en el gen CTLA-4 pueden modificar la habilidad para controlar la proliferación de los linfocitos T, y promover la persistencia o eliminación del virus de la hepatitis C (VHC). Nuestro objetivo fue investigar la frecuencia y asociación de los polimorfismos −319 C/T y +49 A/G del gen CTLA-4, en pacientes con infección por VHC. Métodos: Los polimorfismos del gen CTLA-4 (−319 C/T en la región promotora y +49 A/G en el exón 1) fueron analizados por T-ARMS-PCR en 420 individuos, incluidos 205 pacientes con infección crónica por VHC y 215 sujetos sanos. Resultados: Se encontró una asociación positiva del alelo +49G con la infección por VHC (OR 1,48; IC 95% 1,09-2,02; p=0,02), y con el sexo masculino (OR 1,80; IC 95% 1,16-2,79; p=0,02), ambos en enfermedad crónica (sin cirrosis). Se observaron diferencias significativas en la distribución de los genotipos del polimorfismo +49 A/G, entre los pacientes con infección por VHC y los sujetos sanos en un modelo genético dominante (GG+GA frente a AA; OR1,57; IC 95% 1,05-2,33; p=0,04). No se observaron diferencias en las frecuencias del polimorfismo −319 C/T, entre pacientes con VHC y sujetos sanos. El haplotipo -319C/+49G confiere susceptibilidad a la infección por el genotipo 3 del VHC (OR 10,68; IC 95% 1,17-96,97; p=0,04). Conclusiones: El alelo +49G confiere susceptibilidad a infección por VHC y a infección en el sexo masculino, ambos en enfermedad crónica. Además, el haplotipo -319C/+49G confiere susceptibilidad a la infección por el genotipo 3 del VHC. Nuestros resultados evidencian una implicación importante de los polimorfismos −319 C/T y +49 A/G en la infección por VHC


Introduction and objective: Molecular changes in the CTLA-4 gene can modify the ability to control T lymphocyte proliferation, and promote the persistence or elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in patients infected with HCV. Methods: The CTLA-4 gene polymorphisms (-319 C/T in the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420 individuals, including 205 chronic HCV infected patients and 215 healthy subjects. Results: We found a positive association of +49G allele with HCV infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI 1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant differences in +49 A/G genotypes distribution between HCV infected patients and healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR 1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the -319 C/T polymorphism between HCV infected patients and healthy subjects. Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection (OR 10.68; 95% CI 1.17-96.97; p=.04). Conclusions: The +49G allele confers susceptibility to HCV infection and with male gender, both in chronic disease. In addition, the −319C/+49G haplotype confers susceptibility to HCV genotype 3 infection. Our results support an important role of the −319 C/T and +49 A/G polymorphisms in HCV infection


Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Hepacivirus/pathogenicity , Hepatitis C, Chronic/genetics , CTLA-4 Antigen/genetics , Polymorphism, Genetic/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Case-Control Studies , Haplotypes/genetics , Cross-Sectional Studies
7.
Med Clin (Barc) ; 150(7): 251-256, 2018 04 13.
Article in English, Spanish | MEDLINE | ID: mdl-29033194

ABSTRACT

INTRODUCTION AND OBJECTIVE: Molecular changes in the CTLA-4 gene can modify the ability to control T lymphocyte proliferation, and promote the persistence or elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in patients infected with HCV. METHODS: The CTLA-4 gene polymorphisms (-319 C/T in the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420 individuals, including 205 chronic HCV infected patients and 215 healthy subjects. RESULTS: We found a positive association of +49G allele with HCV infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI 1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant differences in +49 A/G genotypes distribution between HCV infected patients and healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR 1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the -319 C/T polymorphism between HCV infected patients and healthy subjects. Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection (OR 10.68; 95% CI 1.17-96.97; p=.04). CONCLUSIONS: The +49G allele confers susceptibility to HCV infection and with male gender, both in chronic disease. In addition, the -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection. Our results support an important role of the -319 C/T and +49 A/G polymorphisms in HCV infection.


Subject(s)
CTLA-4 Antigen/genetics , Hepatitis C, Chronic/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Young Adult
8.
Endocrinol. nutr. (Ed. impr.) ; 61(2): 87-92, feb. 2014. graf, tab
Article in English | IBECS | ID: ibc-119502

ABSTRACT

BACKGROUND: The body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance. OBJECTIVE: To evaluate the BMI concept across different adiposity magnitudes, in both children and adults. METHODS: We studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass. RESULTS: BMI significantly correlated with percentage of body fat (%BF; children: r = 0.893; adults: r = 0.878) and with total fat mass (children: r = 0.967; adults: r = 0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r = −0.406; p < 0.001) and women (r = −0.413; p < 0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r2 = 0.709), and by a negative correlation of BMI with total fat mass (r = −0.193). CONCLUSIONS: Body weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals


ANTECEDENTES: El índice de masa corporal (IMC) se basa en el concepto original de que el peso corporal aumenta en función de la talla al cuadrado. Como indicador de obesidad, el supuesto actual sobre el IMC es que la adiposidad corporal también aumenta en función de la talla en estados de balance energético positivo. OBJETIVO: Evaluar el concepto del IMC en diferentes magnitudes de adiposidad, tanto en niños como adultos. MÉTODOS: Estudiamos a 975 individuos sometidos a evaluación antropométrica: 474 niños y 501 adultos. Se usó bioimpedancia tetrapolar para evaluar la masa grasa y magra corporal. RESULTADOS: Había una correlación significativa de IMC con el porcentaje de grasa corporal (%GC; niños: r = 0,893, adultos: r = 0,878) y con la masa grasa total (niños: r = 0,967; adultos: r = 0,953). En los niños, el peso corporal, la masa grasa, el %GC y el perímetro de la cintura aumentaban progresivamente en función de la talla al cuadrado. En los adultos, el peso corporal aumentaba en función de la talla al cuadrado, pero el %GC disminuía al aumentar la talla tanto en varones (r = −0,406; p < 0,001) como en mujeres (r = −0,413; p < 0,001). La mayor parte de la varianza del IMC en adultos se explicaba por una correlación positiva de la masa magra total con la talla al cuadrado (r2 = 0,709) y por una correlación negativa del IMC con la masa grasa total (r = −0,193). CONCLUSIONES: El peso corporal aumenta progresivamente en función de la talla al cuadrado. Sin embargo, sólo en los niños la grasa corporal aumenta progresivamente en función de la talla. El IMC no es un indicador ideal de obesidad en los adultos, ya que está significativamente influido por la masa magra, aún en los obesos


Subject(s)
Humans , Male , Female , Child , Adult , Body Composition , Body Weights and Measures/instrumentation , Obesity/diagnosis , Overweight/diagnosis , Body Mass Index , Adipose Tissue
9.
Endocrinol Nutr ; 61(2): 87-92, 2014 Feb.
Article in English, Spanish | MEDLINE | ID: mdl-24388416

ABSTRACT

BACKGROUND: The body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance. OBJECTIVE: To evaluate the BMI concept across different adiposity magnitudes, in both children and adults. METHODS: We studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass. RESULTS: BMI significantly correlated with percentage of body fat (%BF; children: r=0.893; adults: r=0.878) and with total fat mass (children: r=0.967; adults: r=0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r=-0.406; p<0.001) and women (r=-0.413; p<0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r(2)=0.709), and by a negative correlation of BMI with total fat mass (r=-0.193). CONCLUSIONS: Body weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals.


Subject(s)
Body Mass Index , Overweight/diagnosis , Adiposity , Adult , Body Composition , Body Height , Child , Cross-Sectional Studies , Electric Impedance , Female , Humans , Male , Mexico/epidemiology , Middle Aged , Obesity/diagnosis , Obesity/epidemiology , Overweight/epidemiology , Surveys and Questionnaires , Thinness , Waist Circumference , Waist-Hip Ratio
10.
J Nutrigenet Nutrigenomics ; 7(4-6): 212-24, 2014.
Article in English | MEDLINE | ID: mdl-25790965

ABSTRACT

BACKGROUND/AIMS: Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene could explain the adiponectin level. However, the knowledge about the influence of genetic and lifestyle factors is not sufficient. The aim was to analyze whether the effect of the -11391G/A SNP in the ADIPOQ gene is modulated by lifestyle factors in Mexican subjects. METHODS: A cross-sectional study was performed in which 394 participants were analyzed. Genetic, anthropometric, biochemical, dietary, clinical and physical activity parameters were measured. Statistical analysis was performed with SPSSv19 software. RESULTS: The distribution of the -11391G/A SNP genotypes was 55.6 and 44.4% for GG and AG, respectively. The adiponectin level was modulated by the -11391G/A SNP in response to the body mass index (BMI); A allele carriers showed a higher adiponectin level compared to G homozygous carriers but only in the minor BMI tertile group (p=0.032). Adiponectin level variability was explained by gender [(r)=1.5, 95% CI 1.1-1.9, p=0.000], insulin resistance [(r)=-1.2, 95% CI -0.8 to -1.6, p=0.000], physical activity [(r)=0.6, 95% CI 0.2-0.9, p=0.002] and monounsaturated fat intake [(r)=0.5, 95% CI 0.38-1.0, p=0.047]. CONCLUSIONS: The adiponectin level was modulated by the interaction between BMI and -11391G/A SNP; this suggests that the lifestyle rather than genetic factors modulates serum adiponectin.


Subject(s)
Adiponectin/genetics , Polymorphism, Single Nucleotide , Adiponectin/blood , Adolescent , Adult , Aged , Body Mass Index , Cross-Sectional Studies , Female , Gene Frequency , Humans , Insulin Resistance/genetics , Life Style , Male , Mexico , Middle Aged , Nutrigenomics , Obesity/blood , Obesity/genetics , Obesity/pathology , Young Adult
11.
Eur Neurol ; 70(1-2): 117-23, 2013.
Article in English | MEDLINE | ID: mdl-23860493

ABSTRACT

BACKGROUND: The waist-to-height ratio (WHtR) may be a better adiposity measure than the body mass index (BMI). We evaluated the prognostic performance of WHtR in patients with acute ischemic stroke (AIS). METHODS: First, we compared WHtR and BMI as adiposity measures in 712 healthy adults by tetrapolar bioimpedance analysis. Thereafter, baseline WHtR was analyzed as predictor of 12-month all-cause mortality in 821 Mexican mestizo adults with first-ever AIS by a Cox proportional hazards model adjusted for baseline predictors. RESULTS: In healthy individuals, WHtR correlated higher than BMI with total fat mass and showed a higher accuracy in identifying a high percentage of body fat (p < 0.01). In AIS patients a U-shaped relationship was observed between baseline WHtR and mortality (fatality rate 29.1%). On multivariate analysis, baseline WHtR ≤ 0.300 or >0.800 independently predicted 12-month all-cause mortality (hazard ratio 1.91, 95% confidence interval 1.04-3.51). BMI was not associated with mortality, tested either as continuous, binomial or stratified variable. CONCLUSION: WHtR is a modifiable risk factor that accurately demonstrates body fat excess. Extreme WHtR values were associated with increased 12-month all-cause mortality in Mexican mestizo patients with AIS. No survival advantage was found with high WHtR as the pragmatic indicator of obesity in this population.


Subject(s)
Adiposity , Obesity/complications , Stroke/complications , Stroke/mortality , Waist Circumference , Adult , Body Height , Body Mass Index , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Obesity/mortality , Proportional Hazards Models , Risk Factors
12.
Nutrition ; 29(1): 46-51, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22817827

ABSTRACT

OBJECTIVE: To analyze the effect of the fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism on anthropometric and biochemical variables in response to a moderate-fat diet in overweight or obese subjects. METHODS: One hundred nine subjects with a body mass index ≥ 25 kg/m(2) were studied. Participants underwent a dietary intervention that consisted of 30% fat (saturated fat <7% of total calories), 15% protein, and 55% carbohydrates. The FABP2 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Anthropometric and biochemical data were measured at baseline, 1 mo, and 2 mo of nutritional intervention. RESULTS: The mean age was 38.6 ± 11.3 y and the mean body mass index 32.7 ± 6.1 kg/m(2), with 20 men (18%) and 89 women (82%). Fifty-three patients (48.6%) had genotype Ala54Ala (wild-type group) and 56 patients had genotype Ala54Thr/Thr54Thr (51.4%, mutant group). At baseline, no significant difference was found between the FABP2 genotypes groups, except for the carbohydrate intake and resting metabolic rate, which were higher in the Ala54Thr/Thr54Thr group (P < 0.05). At 2 mo, participants had lost 6.8% of their initial weight. The Ala54Thr/Thr54Thr group compared with the Ala54Ala group showed significant decreases in the parameters of weight (-7.5 versus -4.2 kg), body mass index (-2.1 versus -1.2 kg/m(2)), waist circumference (-7.6 versus -5.2 cm), waist-to-hip ratio (-0.04 versus -0.02), and C-reactive protein (-1.4 versus -0.76 mg/L), respectively (P < 0.05). After the resting metabolic rate was adjusted, the decreases in waist circumference, waist-to-hip ratio, and C-reactive protein remained significant between the two groups. CONCLUSIONS: This study showed that the Thr54 allele carriers responded better to a moderate-fat diet.


Subject(s)
Dietary Fats/administration & dosage , Fatty Acid-Binding Proteins/genetics , Obesity/diet therapy , Obesity/genetics , Overweight/diet therapy , Overweight/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Amino Acid Substitution , Anthropometry , Basal Metabolism , Base Sequence , Body Mass Index , Body Weight , DNA/genetics , Fatty Acid-Binding Proteins/metabolism , Female , Humans , Male , Middle Aged , Obesity/metabolism , Obesity/pathology , Overweight/metabolism , Overweight/pathology , Prospective Studies , Waist-Hip Ratio , Young Adult
13.
Alcohol Clin Exp Res ; 36(3): 425-31, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21895718

ABSTRACT

BACKGROUND: Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico. METHODS: Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child's Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant. CONCLUSIONS: In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics.


Subject(s)
Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase/genetics , Cytochrome P-450 CYP2E1/genetics , Liver Cirrhosis, Alcoholic/genetics , Liver Function Tests/statistics & numerical data , Adult , Aldehyde Dehydrogenase, Mitochondrial , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Liver Cirrhosis, Alcoholic/enzymology , Liver Function Tests/methods , Male , Mexico , Polymorphism, Genetic
14.
Salud Publica Mex ; 53 Suppl 1: S37-45, 2011.
Article in Spanish | MEDLINE | ID: mdl-21877071

ABSTRACT

The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed.


Subject(s)
Hepatitis, Viral, Human/epidemiology , Adolescent , Adult , Age Distribution , Aged , Animal Husbandry , Animals , Child , Child, Preschool , Comorbidity , Disease Reservoirs , Endemic Diseases , Female , Health Occupations , Hepatitis, Viral, Human/transmission , Humans , Infant , Male , Mexico/epidemiology , Middle Aged , Occupational Diseases/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Sensitivity and Specificity , Seroepidemiologic Studies , Serologic Tests , Swine/virology , Young Adult
15.
Hepatol Int ; 3(2): 343-55, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19669360

ABSTRACT

To address the relationship between hepatitis B virus (HBV) endemicity and HBV-related liver diseases in Mexico. Research literature reporting on HBsAg and antibody to hepatitis B core antigen (anti-HBc) prevalence in Mexican study groups were searched in NLM Gateway, PubMed, IMBIOMED, and others. Weighted mean prevalence (WMP) was calculated from the results of each study group. A total of 50 studies were analyzed. Three nationwide surveys revealed an HBsAg seroprevalence of less than 0.3%. Horizontal transmission of HBV infection occurred mainly by sexual activity and exposure to both contaminated surgical equipment and body fluids. High-risk groups exposed to these factors included healthcare workers, pregnant women, female sex workers, hemodialysis patients, and emergency department attendees with an HBsAg WMP ranging from 1.05% (95% confidence interval [CI], 0.68-1.43) to 14.3% (95% CI, 9.5-19.1). A higher prevalence of anti-HBc in adults than those younger than 20 years was associated with the main risk factors. Anti-HBc WMP ranged from 3.13% (95% CI, 3.01-3.24) in blood donors to 27.7% (95% CI, 21.6-33.9) in hemodialysis patients. A heterogeneous distribution of HBV infection was detected, mainly in native Mexican groups with a high anti-HBc WMP of 42.0% (95% CI, 39.5-44.3) but with a low HBsAg WMP of 2.9% (95% CI 2.08-3.75). Estimations of the Mexican population growth rate and main risk factors suggest that HBsAg seroprevalence has remained steady since 1974. A low HBsAg prevalence is related to the low incidence of HBV-related liver cirrhosis and hepatocellular carcinoma (HCC) previously reported in Mexico.

16.
Alcohol Clin Exp Res ; 32(4): 559-66, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18241317

ABSTRACT

BACKGROUND: The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis. METHODS: In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non-hyperlipidemic (non-H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR-RFLP's. RESULTS: A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein-cholesterol (HDL-c) was detected in young-aged patients (31.2 +/- 6.2 years old vs. 46.3 +/- 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non-H group. CONCLUSIONS: This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process.


Subject(s)
Alleles , Apolipoprotein E2/genetics , Genetic Linkage/genetics , Hypertriglyceridemia/genetics , Liver Cirrhosis, Alcoholic/genetics , Adult , Age of Onset , Female , Humans , Hypertriglyceridemia/complications , Hypertriglyceridemia/epidemiology , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis, Alcoholic/epidemiology , Male , Middle Aged , Polymorphism, Genetic/genetics
17.
Diab Vasc Dis Res ; 4(3): 235-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17907115

ABSTRACT

Genetic predisposition to cardiovascular risk may vary between different ethnic groups. We studied the effect of the FABP2 A54T polymorphism on biochemical and anthropometric cardiovascular risk factors in 114 obese Mexican subjects. The mean age of the patients studied was 36.8+/-13.3 years. Insulin resistance was present in 47%, hypercholesterolaemia in 49% and hypertriglyceridaemia in 45%. Frequency of the FABP2 genotype was 39% AA, 54.8% AT and 6.2% TT. The AT/TT group showed an increase in body mass index (34+/-7.1 vs. 31+/-4.8 kg/m2), waist circumference (101+/-15.7 vs. 96.5+/-15.8 cm), triglycerides (145+/-60.8 vs. 127+/-79.4 mg/dL; 1.64+/-0.67 vs. 1.43+/-0.89 mmol/L), total cholesterol (176+/-39.4 vs. 164+/-38.2 mg/dL; 4.55+/-1.02 vs. 4.24+/-0.99 mmol/L), LDL (121+/-24.2 vs. 111+/-25.9 mg/dL; 3.13+/-0.62 vs. 2.88+/-0.67 mmol/L) and VLDL (28.8+/-12.1 vs. 25.1+/-16.1 mg/dL; 0.74+/-0.31 vs. 0.64+/-0.41 mmol/L) compared to the AA group (p<0.05). The AT/TT group had greatly increased cardiovascular risk, with an OR of 7.56 (95% CI, 1.82-36.24; p<0.001) compared to the AA group. Our results suggest that A54T polymorphism of the FABP2 gene is associated with cardiovascular disease risk in obese subjects.


Subject(s)
Alleles , Cardiovascular Diseases/genetics , Fatty Acid-Binding Proteins/genetics , Mexican Americans/genetics , Obesity/genetics , Body Mass Index , Cardiovascular Diseases/epidemiology , Genotype , Humans , Hypertriglyceridemia/metabolism , Insulin Resistance , Lipids/blood , Obesity/metabolism , Polymorphism, Genetic , Risk Factors
18.
Liver Int ; 27(7): 930-7, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17696931

ABSTRACT

BACKGROUND: Apolipoprotein AI/apolipoprotein E (apo-AI/apo-E) ratio change and its induction in non-hepatic tissues have been reported during liver development, regeneration, and several pathophysiologic states. The clinical implication of such changes is unclear, but these could reflect recovery and/or severity of liver damage. METHODS AND RESULTS: Using RT-PCR we analysed the mRNA expression of apo-AI and apo-E in peripheral white blood cells (PWBC) of patients with different liver diseases who underwent orthotopic liver transplantation (OLT) and compared its expression with the lipid profile and liver function tests. We found that patients showed higher levels of apo-AI mRNA without detection of apo-E mRNA on PWBC at the preoperative day, compared with healthy volunteers (HV). We found an apo-AI/apo-E mRNA ratio of 2.7 during the anhepatic stage, followed by a decrease to 1.3, 0.95, and 0.55 at days 30, 60, and 90, respectively. At the last time point, the apo-AI/apo-E ratio was similar to HV. At day 3 post-OLT, the lowest levels of high-density lipoprotein (HDL)-cholesterol (17 mg/dl; P<0.05) and the highest levels of aspartate aminotransferase, total bilirubin and alkaline phosphatase (77.5 IU/l, 37.9 g/dl, 177.8 IU/l, respectively; P<0.05) were detected. CONCLUSION: These results indicate that changes of HDL-cholesterol and apo-AI/apo-E mRNA ratio could be a good indicator of liver damage and/or hepatic functional recovery post-OLT.


Subject(s)
Apolipoprotein A-I/blood , Apolipoproteins E/blood , Gene Expression , Leukocytes/metabolism , Liver Diseases/surgery , Liver Transplantation , Liver/physiopathology , RNA, Messenger/blood , Adult , Alkaline Phosphatase/blood , Apolipoprotein A-I/genetics , Apolipoproteins E/genetics , Aspartate Aminotransferases/blood , Bilirubin/blood , Case-Control Studies , Cholesterol, HDL/blood , Female , Humans , Liver/metabolism , Liver Diseases/blood , Liver Diseases/physiopathology , Liver Function Tests , Liver Regeneration , Male , Middle Aged , Recovery of Function , Severity of Illness Index , Time Factors , Treatment Outcome
19.
Biochim Biophys Acta ; 1740(3): 350-6, 2005 Jun 10.
Article in English | MEDLINE | ID: mdl-15949702

ABSTRACT

Because (i) changes in plasma and liver mRNA of apolipoprotein (apo) AI have been observed in patients with alcoholic liver disease, (ii) apo AI mRNA can be induced in non-hepatic tissues, and (iii) apolipoproteins expression is influenced by plasma colloid osmotic pressure (P(CO)) and viscosity (eta), we analyzed the Apo AI mRNA expression in the peripheral white blood cells (PWBC), P(CO), and eta in control volunteers (C), patients with liver cirrhosis (LC), and cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). We found that apo AI mRNA is expressed in the PWBC in 20% of C and it is induced 1.5 fold in 66.6% of LC and 1.95 fold in 85% of LC+AH. A significant decrease of P(CO) in LC and LC + AH (14.8 +/- 2.4 and 16.2 +/- 2.4 mm Hg, respectively) compared to C (27.9 +/- 2 mm Hg) was observed. By contrast, eta was mildly increased from 1.7389 +/- 0.07 in C to 1.8022 +/- 0.154 in LC and 1.9030 +/- 0.177 in LC+AH. No significant correlation was found between P(CO) and eta with apo AI mRNA but with lipid profile. In conclusion, apo AI mRNA expression in PWBC is associated to liver disease severity and could be an indirect indicator of alcoholic liver damage.


Subject(s)
Apolipoprotein A-I/metabolism , Hepatitis, Alcoholic/metabolism , Leukocytes/metabolism , Liver Cirrhosis/metabolism , RNA, Messenger/metabolism , Adult , Analysis of Variance , Apolipoprotein A-I/genetics , Blood Chemical Analysis , Blood Viscosity , DNA , DNA Primers , DNA, Complementary/genetics , Humans , Mexico , Osmotic Pressure
20.
Rev. mex. patol. clín ; 48(1): 7-16, ene.-mar. 2001. ilus, tab, graf, CD-ROM
Article in Spanish | LILACS | ID: lil-310740

ABSTRACT

Introducción: La Retinopatía Diabética (RD) es una de las complicaciones más frecuentes en la diabetes. El factor de riesgo para desarrollar RD en pacientes con diabetes mellitus tipo 2 es más alta en México-Americanos que en blancos no hispánicos, en donde este alto factor de riesgo en México-Americanos es inexplicable. El receptor b3-Adrenérgico (b3-ADR) se expresa en tejido adiposo blanco y café, donde regula los cambios inducidos por la adrenalina y noradrenalina en el metabolismo energético y la termogénesis. Una mutación en el codón 64 del gen b3-AR origina el cambio del aminoácido triptófano (Trp) por arginina (Arg). Los genotipos Trp64Arg y Arg64Arg se han asociado con incremento de triglicéridos y disminución de HDL-c en pacientes con RD proliferativa. Los objetivos fueron investigar la frecuencia y el efecto de los polimorfismos del b3-AR sobre el perfil de lípidos en pacientes con retinopatía diabética no proliferativa (RDNP) del Occidente de México. Métodos: Se incluyeron 31 pacientes con RDNP clasificados de acuerdo a los criterios del ETDRS Research Group y 25 sujetos clínicamente sanos. Se realizó el perfil de lípidos en todos los pacientes y sujetos sanos incluidos en nuestro estudio. Se realizó extracción de DNA a partir de leucocitos de sangre periférica. Se amplificó una región de 248 pb de la región polimórfica (exón 1) del gen b3-AR por PCR. El producto de PCR (248 pb) fue digerido con la enzima de restricción Mva I. Los patrones de restricción, obtenidos por PCR-RFLP's fueron identificados por electroforesis en gel de agarosa teñidos con bromuro de etidio. El análisis estadístico se llevó a cabo usando las pruebas de ANOVA con Tukey y para las variables cualitativas la prueba de c2 y Pearson. Resultados: Se encontraron niveles altos de CT, TG, LDL-c y VLDL-c en pacientes con RDNP comparado con los sujetos sanos (p=0.03; p=0.0001; p=0.002; p=0.0001 respectivamente). Se identificó una asociación entre los genotipos Trp64Arg y Arg64Arg de los pacientes con RDNP y el genotipo Trp64Trp de los sujetos sanos (p=0.0197). No se identificó asociación entre los genotipos del b3-AR y el perfil de lípidos. Conclusión: Nosotros sugerimos que los genotipos Trp64Arg and Arg64Arg pueden contribuir al desarrollo de la RDNP. Los niveles elevados de CT, TG, LDL-c y VLDL-c en pacientes con RDNP es independiente de los genotipos del b3-AR, pero dependientes de la diabetes mellitus tipo 2.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Lipids/analysis , Receptors, Adrenergic, beta , Diabetic Retinopathy/genetics , Genotype , Polymorphism, Genetic
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