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1.
Heliyon ; 10(15): e35477, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39166092

RESUMO

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

2.
Biomed Pharmacother ; 162: 114649, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37023620

RESUMO

Epidemiological studies imply there is a higher risk of cardiovascular disease in menopausal women. Some explanations suggest a lack of estrogens as the cause, but estrogens do not disappear completely and are just transformed into different products called estrogenic degradation metabolites (EDMs). When estrogens are metabolized, reactive oxygen species (ROS) increase, causing DNA damage and increasing oxidative stress. These conditions are associated to neurodegenerative diseases and different types of cancer. However, their effect on the cardiovascular system remains unknown. This paper compares estrogenic metabolite levels in serum from post-menopausal women with cardiovascular risk (CAC>1) and with establish cardiovascular disease (CVD), against levels in healthy women (Ctrl). Sample sera were obtained from the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Serum levels of eleven estrogenic metabolites were quantified by High performance liquid chromatography (HPLC) and oxidative stress markers such as ROS, lipoperoxidation levels (TBARS), total antioxidant capacity (TAC), super oxide dismutase activity (SOD) and cytokine levels were evaluated. 8-hydroxy-2-deoxyguanosine (8-OHdG) was also determined as a marker of nuclear damage.There were significant differences between serum levels of some EDMs in CAC> 1 and CVD vs. serum levels in Ctrl women. Results also revealed an increase in oxidative stress and a diminished capacity to manage oxidative stress. These findings provide an overview, and suggest that some estrogenic metabolites may be associated with an increased risk of CVD in menopausal women. However, additional studies are needed to evaluate the impact of these EDMs directly on cardiovascular function.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Feminino , Humanos , Estrogênios/metabolismo , Doenças Cardiovasculares/etiologia , Espécies Reativas de Oxigênio , Menopausa
3.
Arterioscler Thromb Vasc Biol ; 41(9): 2494-2508, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34233476

RESUMO

Objective: Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. Approach and Results: A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. Conclusions: This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.


Assuntos
HDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Hiperlipoproteinemia Tipo II/genética , Proteínas de Transporte de Nucleotídeos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idade de Início , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Células HEK293 , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Análise da Randomização Mendeliana , México/epidemiologia , Camundongos , Pessoa de Meia-Idade , Proteínas de Transporte de Nucleotídeos/metabolismo , Fenótipo , Medição de Risco
4.
Ther Adv Endocrinol Metab ; 11: 2042018820943374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782778

RESUMO

BACKGROUND AND AIMS: To the best of our knowledge, no studies have investigated the metabolic control of patients with premature coronary artery disease (CAD). The present study analyzes the metabolic control, defined as the simultaneous target in blood pressure, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c, as well as the factors associated with its achievement in patients with premature CAD. METHODS: The study included 1206 patients with CAD diagnosed before the age of 55 and 65 years in men and women, respectively. Sociodemographic, clinical and biochemical data were collected to know the prevalence of cardiovascular risk factors, including individual components of metabolic control plus smoking cessation and body mass index (BMI) <25 kg/m2. Non-strict and strict targets were used to evaluate metabolic control. RESULTS: Participants were 54 ± 8 years old, 19.7% were women and had a median CAD evolution of 2.4 years. Non-strict and strict metabolic control was achieved by 18.4% and 6.2% of patients, respectively. Moreover, 79.8% and 67.6% met a composite of three or more cardiovascular risk factor goals using both criteria. BMI <25 kg/m2 was independently associated with 1.734 (95% confidence interval: 1.207-2.492) and 2.541 (95% confidence interval: 1.608-4.014) higher probabilities to meet non-strict or strict metabolic control. CONCLUSION: Our results show that 18.4% and 6.2% of subjects with premature CAD achieved non-strict and strict metabolic control, respectively. BMI <25 kg/m2 was found to be associated with the achievement of metabolic control. Multidisciplinary strategies including healthy lifestyle changes and pharmacological therapies could decrease the socioeconomic and clinical impact of premature CAD.

5.
J Clin Hypertens (Greenwich) ; 22(7): 1253-1262, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32644257

RESUMO

High blood pressure (BP) is the major cardiovascular-risk factor for coronary artery disease (CAD), principally in young patients who have an important and increasing socioeconomic burden. Despite the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), recommended BP target <140/90 mm Hg for patients with stable CAD, in 2017 the American College of Cardiology and the American Heart Association (ACC/AHA) updated BP target to <130/80 mm Hg. We aimed to analyze the prevalence of BP control in patients with premature CAD using both criteria. In addition, antihypertensive therapy, lifestyle, clinical, and sociodemographic characteristics of the patients were evaluated in order to identify factors associated with the achievement of BP targets. The present study included 1206 patients with CAD diagnosed before 55 and 65 years old in men and women, respectively. Sociodemographic, clinical, and biochemical data were collected. The results indicate that 85.6% and 77.5% of subjects with premature CAD achieved JNC-7 non-strict and ACC/AHA strict BP target, respectively. Consistently, number of antihypertensive drugs and hypertension duration >10 years were inversely associated with BP targets, whereas total physical activity and smoking were directly associated with BP targets, regardless of BP criteria. Considering that age, gender, and hypertension duration are non-modifiable cardiovascular-risk factors, our results highlight the need for more effective strategies focused on increase physical activity and smoking cessation in young patients with CAD. These healthier lifestyles changes should favor the BP target achievement and reduce the socioeconomic and clinical burden of premature CAD.


Assuntos
Doença da Artéria Coronariana , Hipertensão , Idoso , American Heart Association , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/prevenção & controle , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estados Unidos
6.
Rev Invest Clin ; 72(1): 19-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32132739

RESUMO

BACKGROUND: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). OBJECTIVE: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. METHODS: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. RESULTS: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. CONCLUSION: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.


Assuntos
Síndrome Coronariana Aguda/genética , RNA Helicases DEAD-box/genética , Infarto do Miocárdio/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Linfotoxina-alfa/genética , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
7.
Rev. invest. clín ; Rev. invest. clín;72(1): 19-24, Jan.-Feb. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1251830

RESUMO

ABSTRACT Background: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). Objective: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. Methods: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. Results: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. Conclusion: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , RNA Helicases DEAD-box/genética , Síndrome Coronariana Aguda/genética , Infarto do Miocárdio/genética , Estudos de Casos e Controles , Linfotoxina-alfa/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Adaptadoras de Transdução de Sinal/genética , Frequência do Gene , Genótipo , México
8.
Int J Obes (Lond) ; 44(4): 920-928, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31792333

RESUMO

OBJECTIVE: To use the combined presence of the elevated insulin resistance index in adipose tissue (Adipo-IR) and low values of adiponectin as a marker of dysfunctional adipose tissue, and to analyze its possible association with low values of high-density lipoprotein cholesterol (HDL-C) and small size of HDL particles. RESEARCH DESIGN AND METHODS: The analysis included 253 subjects with functional adipose tissue and 253 with dysfunctional adipose tissue, considering similar gender, age, and body mass index (BMI). Adipo-IR was considered when index values (free fatty acids × insulin concentrations) were ≥75th percentile. Low levels of adiponectin were considered when concentration in serum was <25th percentile (determined by ELISA). HDL size was estimated by a quantitative validated equation. Small HDL size was considered when values were <25th percentile. RESULTS: When comparing subjects with functional adipose tissue with those of dysfunctional adipose tissue, the latter had a higher prevalence of low HDL-C (51.4% vs. 64.0%; p = 0.004) and small HDL (56.9% vs. 67.6%; p = 0.009). Multivariate analysis indicated that independently from other metabolic risk factors, dysfunction of adipose tissue is significantly associated with low HDL-C (OR: 1.624 [CI 95%: 1.100-2.397]) and small HDL (OR: 1.462 [CI 95%: 1.000-2.139]). Adding BMI, waist circumference, and subcutaneous or visceral adipose tissue did not modify the association. CONCLUSIONS: Dysfunction of adipose tissue is associated with a 65 and 50% higher probability of having low HDL-C and small HDL. Identification of dysfunctional adipose tissue could be a useful tool in the clinical setting to prevent the cardiometabolic risk independently from adiposity.


Assuntos
Tecido Adiposo Branco , HDL-Colesterol , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/fisiopatologia , Índice de Massa Corporal , Peso Corporal/fisiologia , HDL-Colesterol/sangue , HDL-Colesterol/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Tamanho da Partícula , Circunferência da Cintura/fisiologia
9.
Front Genet ; 10: 530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214252

RESUMO

DNA damage and subsequent repair pathways have been involved in the initiation and progression of atherosclerosis. Meiotic recombination 11 homolog A (MRE11A) gene polymorphisms have been associated with the presence of myocardial infarction. We analyzed five MRE11A gene polymorphisms in 386 individuals with subclinical atherosclerosis and 1093 healthy controls. Under different models, the rs13447720 (Odds ratio = 0.646, Padditive = 0.009; Odds ratio = 0.636, Pdominant = 0.012; Odds ratio = 0.664, Pover-dominant = 0.025; Odds ratio = 0.655, Pcodominant1 = 0.021) and rs499952 (Odds ratio = 0.807, Padditive = 0.032; Odds ratio = 0.643, Pcodominant2 = 0.034) polymorphisms were associated with a lower risk of subclinical atherosclerosis. On the other hand, the rs2155209 polymorphism was associated with a reduced risk of having a coronary artery calcification score ≥ 100 Agatston units. The rs13447720, rs499952, and rs2155209 polymorphisms, as well as the haplotypes that included the five studied polymorphisms were associated with some clinical and metabolic parameters in both subclinical atherosclerosis and healthy individuals. Our results suggest that the rs13447720 and rs499952 polymorphisms are associated with a decreased risk of developing subclinical atherosclerosis, whereas the rs2155209 is associated with a lower subclinical atherosclerosis severity (coronary artery calcification < 100 Agatston units). MRE11A polymorphisms and haplotypes were associated with clinical and metabolic parameters.

10.
Genet Mol Biol ; 42(3): 519-525, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31188921

RESUMO

Polymorphisms in the LPA gene have been associated with aortic valve calcification (AVC). There are wide differences in the allelic frequencies, Lp(a) levels, and the association with AVC among ethnic groups. The aim of this study was to determine the association of the LPA gene polymorphisms with Lp(a) levels and risk of developing AVC, in Mexican-Mestizos population. Six LPA polymorphisms (rs10455872, rs7765803, rs6907156, rs1321195, rs12212807 and rs6919346) were genotyped by TaqMan assays in 1,265 individuals without premature coronary artery disease. The presence of AVC was determined by computed tomography. The association of the LPA polymorphisms with AVC, Lp(a), and other cardiovascular risk factors (CVRF) was evaluated using logistic regression analysis. Compared to AA genotype, subjects with AG+GG genotypes had high prevalence of Lp(a) ≥ 30 mg/dL (7.1% vs. 23.7%, p<0.001) and AVC (19.0% vs. 29.4%, p=0.007). In a model adjusted for several CVRF, the LPA rs10455872-G allele was associated with high Lp(a) levels and AVC. Carriers of G allele had a high risk of Lp(a) ≥ 30 mg/dL (OR= 3.86, CI 95%: 2.2 - 6.7, p=0.001) and AVC (OR= 2.54, CI 95%: 1.56 - 4.14, p=0.001), independently of other CVRF. In this population, carriers of rs10455872-G allele had 3.86 and 2.54 higher risk of Lp(a) ≥ 30 mg/dL or presence of AVC, respectively.

11.
Cytokine ; 114: 32-37, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30594065

RESUMO

Our previous data suggest that the heterodimeric interleukin-27 (IL-27) could participate in the developing of insulin resistance (IR). Our aim was to assess the participation of IL-27p28 gene single nucleotide polymorphisms (SNPs) as markers for IR, subclinical atherosclerosis (SA) and cardiovascular risk factors in a Mexican population. Five IL-27p28 SNPs (rs153109, rs40837, rs17855750, rs26528 and rs181206) were genotyped in 856 individuals with IR and 644 participants without IR. Under inheritance models adjusted for confounding factors, the rs153109A (0.78[0.64-0.94] Padditive = 0.008, 0.58[0.41-0.82] Precessive = 0.002, 0.57[0.38-0.83] Pcodominant2 = 0.004), rs26528T (0.78[0.64-0.94] Padditive = 0.008, 0.61[0.43-0.88] Precessive = 0.007, 0.57[0.38-0.84] Pcodominant2 = 0.004) and rs40837A (0.76[0.63-0.92] Padditive = 0.004; 0.60[0.42-0.86] Precessive = 0.005; 0.54[0.37-0.80] Pcodominant2 = 0.002) alleles were related with a decreased risk of IR. Moreover, AAATA haplotype that contains the protector alleles was related with 17% lower risk of presenting IR (0.83 [0.71-0.98], P = 0.023). After adjusting for potential confounding variables, IL-27p28 SNPs were not associated with SA. However, some SNPs were associated with hypertension (rs26528 and rs40837) and increased total abdominal fat (rs17855750) in non-IR individuals, whereas in IR subjects we observed an association of rs26528 and rs40837 with hypoadiponectinemia. Our evidence suggests that rs40837A, rs153109A, and rs26528T alleles could be envisaged as protective markers for IR. Some polymorphisms showed an association with hypertension, low adiponectin levels, and increased total abdominal fat.


Assuntos
Aterosclerose/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Resistência à Insulina/genética , Interleucina-27/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Haplótipos/genética , Humanos , Masculino , México , Pessoa de Meia-Idade , Fatores de Risco
12.
Immunobiology ; 224(1): 10-14, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30501958

RESUMO

The aim of this study was to evaluate the association of rs1805193, rs5361, and rs5355 E-selectin gene single nucleotide polymorphisms (SNPs) with the risk of developing subclinical atherosclerosis (SA) in a group of Mexicans individuals. SNPs were determined by TaqMan genotyping assays in a group of 287 individuals with SA and 688 healthy controls. Under different models, the T allele of the 5'UTR G98 T (rs1805193) (OR = 1.71, 95%CI: 1.00-2.93, pCCo-dominant = 0.0006, OR = 2.02, 95%CI: 1.21-3.38, pCDominant = 0.004, and OR = 2.14, 95%CI: 1.34-3.44, pCAdditive = 0.0015) and the C allele of the Ser128Arg A561C (rs5361) (OR = 1.60, 95%CI: 0.92-2.79, pCCo-dominant = 0.012, OR = 1.78, 95%CI: 1.04-3.06, pCDominant = 0.038, and OR = 1.87, 95%CI: 1.13-3.11, pCAdditive = 0.016) polymorphisms were associated with an increased risk of development of SA. In the same way, under co-dominant model, the CT genotype of the Leu575Phe C1880T (rs5355) polymorphism was associated with an increased risk of SA as compared to CC genotype (OR = 2.34, 95%CI: 1.33-4.11, pC = 0.0035). All models were adjusted by traditional cardiovascular risk factors. In summary, this study demonstrates that the 5'UTR G98 T, Ser128Arg A561C, and Leu575Phe C1880T polymorphisms are associated with an increased risk of developing SA.


Assuntos
Aterosclerose/genética , Selectina E/genética , Genótipo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
13.
Int J Cardiol ; 279: 168-173, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30305239

RESUMO

BACKGROUND: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. METHODS: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. RESULTS: Only two loci were associated with SUA levels: SLC2A9 (ß = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (ß = 0.23 mg/dl, P = 2.42 × 10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. CONCLUSIONS: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , México/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
14.
Mol Genet Genomic Med ; 7(1): e00509, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30549243

RESUMO

BACKGROUND: The aim of this study was to establish the association of two polymorphisms of the ß-defensin 1 gene (DEFB1, OMIM#602056) with the risk of developing type 2 diabetes mellitus (T2DM) in a group of Mexican patients. METHODS: The 5'UTR -20 G/A, and -44 C/G polymorphisms of DEFB1 gene were genotyped by 5' exonuclease TaqMan assays in a group of 252 patients with T2DM and 522 healthy control. RESULTS: Under dominant and additive models adjusted for the risk factors, the C allele of the -44 C/G polymorphism was associated with increased risk of T2DM (OR = 1.63, 95% CI = 1.07-2.48, pCdom  = 0.021 and OR = 1.42, 95% CI = 1.05-1.91, pCadd  = 0.023, respectively). In addition, the linkage disequilibrium analysis showed that AC haplotype was associated with an increased risk of developing T2DM (OR = 4.39, p = 0.04). The in-silico analysis showed that the -44 C allele produces a binding site for the transcription factor Ikaros (IK). CONCLUSION: This study demonstrates that the C allele of -44 C/G polymorphism, as well as haplotype AC are associated with the presence of T2DM in the Mexican population. The variation in this polymorphism of the DEFB1 gene could increase the migration of the macrophages to pancreatic islets accelerate the ß-cell dysfunction in T2DM.


Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , beta-Defensinas/genética , Idoso , Sítios de Ligação , Feminino , Haplótipos , Humanos , Fator de Transcrição Ikaros/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica , beta-Defensinas/química , beta-Defensinas/metabolismo
15.
Inflamm Res ; 68(3): 215-221, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30560371

RESUMO

OBJECTIVE: The aim of the study was to evaluate the association of miRNA-146a G/C (rs2910164), and miRNA-196a2 C/T (rs11614913) polymorphisms with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. MATERIALS AND METHODS: The polymorphisms were determined in 218 patients with CAD who underwent coronary artery stenting (66 with restenosis and 152 without restenosis) and 611 healthy controls using 5' exonuclease TaqMan assays. RESULTS: The distribution of both polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant and additive genetic models, the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism was associated with increased risk of CAD (OR = 2.18, Pco-dom = 0.006, OR = 1.86, Pdom = 0.002, and OR = 1.52, Padd = 0.002, respectively). All models were adjusted for age, type 2 diabetes mellitus, dyslipidemia, hypertension and smoking habit. The "GT" haplotype was associated with increased risk of developing CAD (OR = 1.36, P = 0.046). CONCLUSIONS: Our data suggests that the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism is associated with the risk of developing CAD, but no association with restenosis was observed.


Assuntos
Doença da Artéria Coronariana/genética , Reestenose Coronária/genética , MicroRNAs/genética , Stents , Idoso , Doença da Artéria Coronariana/terapia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
16.
Rev Invest Clin ; 70(6): 301-309, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532096

RESUMO

BACKGROUND: In subjects without a history of coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) is associated with carotid artery plaques (CAP), which is a better marker than high carotid intima-media thickness (hCIMT) for predicting first or recurrent cardiovascular events. OBJECTIVE: The objective of this study is to analyze the association of T2DM with CAP and hCIMT in premature CHD patients. METHODS: Premature CHD was considered before the age of 55 years in men and before 65 in women. T2DM was defined according to the American Diabetes Association criteria. CAP was defined as a focal structure encroaching the arterial lumen by at least 50% of the surrounding IMT value or with a thickness > 1.5 mm. RESULTS: Among 1196 patients (CHD duration 1.5 years [interquartile range: 0.4-5.6]), 37.2% had T2DM, and 97.8% were on antihypertensive, 94.4% on lipid-lowering, and 97.3% on anti-aggregate treatment. hCIMT prevalence was similar in patients with or without T2DM, whereas CAP prevalence was higher among T2DM patients (17.7% vs. 30.9%; p < 0.001). T2DM showed association with CAP, independently of CHD evolution and glycemic control (odds ratio: 1.57; 95% confidence interval: 1.09-2.26). CONCLUSIONS: T2DM has an independent association with CAP. Early detection of recurrent cardiovascular events, with CAP identification, could be useful to prevent complications in patients with CHD.


Assuntos
Espessura Intima-Media Carotídea , Estenose das Carótidas/epidemiologia , Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Adulto , Fatores Etários , Idoso , Estenose das Carótidas/diagnóstico , Doença das Coronárias/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Fatores Sexuais
17.
Genet Mol Biol ; 41(2): 371-378, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29786102

RESUMO

We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.

18.
Ann Hepatol ; 17(3): 419-425, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29735791

RESUMO

INTRODUCTION AND AIM: Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS: Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS: The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS: In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.


Assuntos
Fígado Gorduroso/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Ingestão de Energia , Exercício Físico , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
19.
Gene ; 663: 34-40, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655894

RESUMO

Several studies have reported the role of hedgehog interacting protein-like 1 (HHIPL-1) in different pathologies, including cardiovascular disease. The aim of the present study was to analyze the association of HHIPL-1 (rs2895811) polymorphism with myocardial infarction (MI), cardiometabolic parameters, and traditional cardiovascular risk factors in the Mexican population. The polymorphism was genotyped using a TaqMan assay in 1023 patients with MI and 1105 controls. A similar distribution of the polymorphism was observed between studied groups. However, in patients group, the C allele was associated with a decreased risk of developing hypertriglyceridemia (OR = 0.757, Padditive = 0.030, OR = 0.685, Pdominant = 0.020, OR = 0.691, Pcodominant1 = 0.030), metabolic syndrome (OR = 0.746, Padditive = 0.030, OR = 0.647, Pdominant = 0.005, OR = 0.670, Pheterozygote = 0.015, OR = 0.637, Pcodominant1 = 0.005), and insulin resistance (OR = 0.681, Pdominant = 0.045). The results suggest that HHIPL-1 rs2895811 polymorphism is associated with cardiometabolic parameters in Mexican patients with MI.


Assuntos
Hipertrigliceridemia/genética , Resistência à Insulina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Síndrome Metabólica/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Fatores de Risco
20.
Lipids ; 53(2): 157-166, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29570220

RESUMO

We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.


Assuntos
Síndrome Coronariana Aguda/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Lipoproteínas HDL/genética , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
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