Genetic and Oral Tests for the Diagnosis of Lactose Intolerance in Mixed-Ancestry Brazilians with Metabolic Syndrome.

BACKGROUND/AIMS: Metabolic syndrome (MetS) comprises a cluster of physiological and anthropometric abnormalities. MetS has been linked to lactose intolerance (LI). The aim of this study was to compare the sensitivity and specificity to detect LI using 2 different tests: (1) a genetic test and (2) an oral lactose tolerance test (OLTT). METHODS: Two hundred and fifty-four MetS patients, ≥20 years of age, of both genders, were recruited for this comparative study. Nine single nucleotide polymorphisms (SNPs) were selected for genetic investigation: rs182549and rs4988235(both considered "gold standard"); rs56064699; rs148142676; rs562211644; rs59533246; rs3754689; rs2278544,and rs10552864(as potential novel SNPs). Sensitivity and specificity, as well as positive and negative predictive values, were calculated for each genotype using WINPEPI version 11.65. Differences between positive and negative OLTT groups were considered statistically significant when p ≤ 0.05. RESULTS: Among the selected SNPs, only rs182549(p < 0.001) and rs4988235(p < 0.001) gave similar results compared to an OLTT. The sensitivity of both SNPs to detect LI was 87 and 86%, and specificity was 83 and 82.5%, respectively. CONCLUSION: Genetic tests using rs182549and rs4988235SNPs showed high agreement with OLTT. These genetic tests may be a good option to replace OLTT in MetS patients.

Tempo de trânsito intestinal de indivíduos portadores de síndrome metabólica pela escala de bristol / Intestinal transit time of individuals with metabolic syndrome by the bristol scale

Introdução: a síndrome Metabólica (SM) é um transtorno de origem multifatorial que envolve a elevação da circunferência da cintura, da glicemia, da pressão arterial e dos triglicerídeos e redução do HDL-colesterol. Na etiopatogenia deste transtorno, diversos fatores genéticos e ambientais estão envolvidos, dentre eles, a alteração da microbiota intestinal pode ser um dos agentes causais deste distúrbio. Devido aos elevados custos para analisar este ecossistema, e à sua impossibilidade na prática clínica, ferramentas podem ser utilizadas com a intenção de monitorar o funcionamento intestinal, a exemplo da Escala de Bristol. Metodologia: foram avaliados indivíduos adultos e idosos com Síndrome Metabólica atendidos entre fevereiro de 2015 e maio de 2017. A síndrome metabólica foi definida de acordo com o preconizado pela Federação Internacional de Diabetes. Foi realizada anamnese com informações a respeito da consistência das fezes e coleta de medidas clínicas e antropométricas. Foi realizada análise estatística descritiva. Resultados: foram incluídos neste estudo 186 pacientes, com predominância do sexo feminino (83,9%) e indivíduos adultos (55,1%). Dentre os critérios da SM, o mais presente foi a pressão arterial elevada (95,1%), e a maior parte dos indivíduos apresentaram ritmo intestinal normal pela Escala de Bristol (54,8%). Em relação à idade entre os grupos, o que apresentou ritmo lento, teve maior média de idade (69 anos) em relação aos grupos com ritmo normal e ritmo rápido (57 e 54 anos, respectivamente). Por sua vez, indivíduos com ritmo intestinal rápido, apresentaram maiores médias de índice de massa corporal. Conclusão: indivíduos com Síndrome Metabólica parecem possuir tempo de trânsito intestinal adequado segundo a Escala de Bristol.

Introduction: metabolic syndrome (MS) is a multifactorial disorder that involves elevation of waist circumference, blood glucose, blood pressure and triglycerides, and reduction of HDL-cholesterol. In the etiopathogenesis of this disorder, intestinal health plays an important role, especially in the composition of the microbiota. Due to the high costs to analyze this ecosystem, and the impossibility in clinical practice, other tools can be used with the intention of monitoring the state of health of the microbiota such as the Bristol Scale. Metodology: adult and elderly individuals attended at the Núcleo de Pesquisa e Extensão em Genômica Nutricional e Disfunções Metabólicas of Universidade do Estado da Bahia between February 2015 and May 2017 were evaluated. Anamnesis was performed with information about the consistency of feces and Collection of clinical and anthropometric measurements. The metabolic syndrome was defined according to the International Diabetes Federation. Data were analyzed descriptively. Results: a total of 186 patients were analyzed during the study period, with a predominance of females (83.9%) and adults (55.1%). Among the criteria of MS, the most present was high blood pressure (95.1%), and most of the individuals presented normal bowel rhythm by the Bristol Scale (54.8%). In relation to the age between the groups, which presented a slow rhythm, the mean age (69 years) was higher in relation to the groups with normal rhythm and fast rhythm (57 and 54 years, respectively). In turn, individuals with fast bowel rhythm presented higher mean body mass index. Conclusion: individuals with Metabolic Syndrome seem to have intestinal transit time according to the Bristol Scale.

Associação entre níveis séricos de vitamina D e componentes da síndrome metabólica em pacientes atendidos no centro de estudos e atendimento dietoterápico da Universidade do Estado da Bahia / Association between serum levels of vitamin D and components of the metabolic syndrome in patients attended at the Center for Studies and Diet Therapy at the State University of Bahia

Introdução: a síndrome metabólica é um conjunto de disfunções que ocorre no metabolismo. Por sua vez, as disfunções endocrinometabólicas, incluindo componentes da síndrome, tais como obesidade, diabetes mellitus, elevação da pressão arterial e dislipidemias, têm sido associadas a baixos níveis séricos de vitamina D. A Hipovitaminose D tem atingido altas prevalências em diferentes populações mundiais, sobretudo em portadores desta síndrome. Metodologia: estudo observacional analítico, descritivo, de corte transversal. Os pacientes foram diagnosticados com síndrome metabólica a partir das recomendações da IDF, 2006. A coleta de dados foi realizada no período de agosto de 2015 a julho de 2016 e para determinação da concentração sérica de 25-hidroxivitamina D foi utilizado o método de quimioluminescência. Resultados: a hipovitaminose D foi observada em 77,6% dos pacientes. Dentre os componentes da SM a hipertensão arterial foi o mais prevalente. A análise de dados evidenciou correlação inversamente proporcional entre os níveis séricos de 25(OH)D, com as medidas de circunferência da cintura (r= ­ 0,245; pvalor= 0,013), com níveis séricos de triglicerídeos (r= ­ 1,54; pvalor= 0,030) e também com valores de Índice de Massa Corporal (r= ­ 0,225; pvalor= 0,023). Conclusão: neste estudo foi observado alta prevalência de hipovitaminose D e evidenciada correlação inversa entre os níveis séricos de vitamina D e as medidas de Circunferência da Cintura, de níveis séricos de triglicerídeos e valores de IMC.

Introduction: metabolic syndrome is a condition in which the individual manifests a set of metabolic dysfunctions. Endocrine-metabolic dysfunctions, including components of the syndrome, such as diabetes mellitus, elevated blood pressure and dyslipidemias, have been associated with low serum levels of vitamin D. Hypovitaminosis D has reached high prevalence in different world populations, Patients with this syndrome. Metodology: descriptive, cross-sectional observational study. Patients were diagnosed with metabolic syndrome from the recommendations of the IDF, 2006. Data collection was performed from August 2015 to July 2016 and for determination of the serum concentration of 25-hydroxyvitamin D was used the chemiluminescence method. Results: hypovitaminosis D was observed in 77.6% of the patients. Among the components of MS, arterial hypertension was the most prevalent. Data analysis showed an inversely proportional correlation between 25 (OH) D serum levels and waist circumference (r = ­ 0.245; pvalor = 0.013), with serum triglyceride levels (r = ­ 1.54; pvalor = 0.030) and also with values of Body Mass Index (r = ­ 0.225, pvalor = 0.023). Conclusion: in this study, a high prevalence of D-hypovitaminosis was observed and an inverse correlation was found between serum vitamin D levels and Waist Circumference, serum triglyceride levels and BMI values.

Case-control association study of polymorphisms in the angiotensinogen and angiotensin-converting enzyme genes and coronary artery disease and systemic artery hypertension in African-Brazilians and Caucasian-Brazilians.

The rennin-angiotensin-aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is also related to this pathology. This investigation aimed to analyse if the frequencies of AGT M235T (rs699) and ACE I/D (rs4646994) polymorphisms are associated with CAD and SAH in African-Brazilians and Caucasian-Brazilians. In this study we analysed 714 subjects who underwent coronary angiography to detect obstructive lesions and CAD, as well as blood pressure measurement and SAH, grouped according to ethnicity: 266 African-Brazilians and 448 Caucasian-Brazilians. Among CAD and SAH cases and controls, the genotype and allele frequencies of ACE I/D polymorphism were similar in both ethnic groups. The AGT 235TT genotype and 235T allele frequencies were higher in SAH cases (32%, 54.7%) versus controls in Caucasian-Brazilians (19.8%, 46.4%; P = 0.038, P = 0.031, respectively). The AGT 235TT (OR = 1.8; P = 0.028) demonstrated to be an independent factor risk in a multivariate logistic regression increasing SAH risk in Caucasians but not in African-Brazilians. In summary, AGT M235T polymorphism was associated with SAH risk in Caucasian-Brazilians, and no association was detected with CAD. No association was also observed in ACE I/D polymorphism either in CAD or SAH in African-Brazilians and Caucasian-Brazilians.

Interleukin-1 beta and interleukin-6 gene polymorphism associations with angiographically assessed coronary artery disease in Brazilians.

The inflammatory process has been considered an important mediator for the development of atherosclerosis. Interleukin-1 beta (IL1B) is a precursor of interleukin-6 (IL6) in the acute phase of inflammatory response and their levels are elevated in patients with coronary artery disease. The aim of the present study was to further investigate the association of IL-1B and IL-6 gene polymorphisms and angiographically assessed coronary artery disease (CAD) in African- and Caucasian-Brazilians. This report analyzed the IL-1B-511C>T and IL-6-174G>C polymorphisms in 667 patients (253 African-Brazilians and 414 Caucasian-Brazilians) who underwent coronary angiography. Patients with a coronary obstructive lesion 50% presented a higher frequency of the IL-1B-511CC genotype (30.4%) compared to lesion-free individuals (16.5%, p=0.032) in African- but not in Caucasian-Brazilians. No significant genotype frequency difference was identified for the IL-6-174G>C polymorphism in either ethnic groups. However, after correction for other CAD risk factors using multivariate logistic regression, both the IL-1B-511CC [Odds ratio (OR)=2.3; p=0.019] and the IL-6-174GG (OR=2.0; p=0.028) genotypes were considered independent CAD risk predictors in African-Brazilians. This report shows that the IL-1B-511C>T and IL-6-174G>C polymorphisms were associated with CAD risk in African-Brazilians and no association was detected among Caucasian-Brazilians.

Correlation between polymorphisms at interleukin-6 but not at interleukin-10 promoter and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis in Brazilian individuals.

HTLV-1 is the etiologic agent of ATL and HAM/TSP. The majority of HTLV-1-infected individuals remain asymptomatic, indicating that the infection alone is not sufficient to cause the diseases. It has been reported that cytokine gene polymorphisms, including polymorphisms at IL-6 and IL-10 gene, might be important. We analyzed SNP in the promoter region of the IL-6: -174, -572, -597, and -634 positions, and IL-10: -592 position to evaluate the role of these polymorphisms in the HAM/TSP pathogenesis in 133 HTLV-1 infected individuals and in 100 healthy individuals from Salvador, Bahia, Brazil. The -634C allele frequencies were higher among HAM/TSP patients (21.2%) than among oligosymptomatic (6.5%; P = 0.038) and asymptomatic (9.5%; P = 0.025) subjects. Similarly, the -174G allele frequencies were higher in HAM/TSP patients than in oligosymptomatic patients (P = 0.02). Moreover, the -634GC/-174GG genotype combination was identified at a higher frequency (38.5%) in the HAM/TSP patients than in subjects with other clinical status (8.7%; P = 0.016 for oligosymptomatic and 15.5%, P = 0.012 for asymptomatic patients). However, the multivariate logistic regression including the genotypes of the three studied loci showed that only -634 C IL-6 carriers remain as significant and independent TSP/HAM predictor (odds ratio [OR] = 5.31; 95% [CI] = 1.60-17.56; P = 0.006). We suggest that -634 G C in IL-6 could contribute to HAM/TSP development and that identification of the collective influence of several cytokine polymorphisms, their prevalence, and their interaction could help to better understand this disease.

Sex-specific effect of the thermolabile C677T mutation in the methylenetetrahydrofolate reductase gene on angiographically assessed coronary artery disease in Brazilians.

Hyperhomocysteinemia is associated with increased coronary artery disease (CAD) risk. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine and presents a common mutation (C677T) that leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased CAD risk. The C677T MTHFR mutation was studied in 772 subjects (480 Caucasian Brazilians and 292 African Brazilians) who underwent coronary angiography at the hemodynamic center of the Santa Izabel Hospital in Salvador, Bahia State, Brazil. The 677T allele frequency was increased in Caucasian Brazilians (28.1%) compared to the frequency observed in African Brazilians (18.3%; p < 0.001). In Caucasian Brazilians the frequency of the 677T homozygous genotype was increased in CAD cases (10.4%) compared to control subjects (1.4%; p = 0.014) in males but not in females. In African Brazilians the mutation was not associated with CAD in either sex. The multivariate logistic regression analysis of all the samples shows that the 677T homozygous interaction with sex was a significant CAD predictor, independent of other classical risk factors and ethnic group. The odds ratio associated with male 677T homozygotes was increased 9.2-fold (p = 0.021) compared to the 677C carriers. The present study suggests that the C677T MTHFR mutation is associated with increased CAD risk in a sex-dependent manner in Brazilians.

Paraoxonase 1 gene polymorphisms in angiographically assessed coronary artery disease: evidence for gender interaction among Brazilians.

BACKGROUND: Paraoxonases (PON) are members of an enzyme family involved in preventing low-density lipoprotein oxidation and therefore protecting against atherosclerotic plaque formation. METHODS: We studied the Met55Leu and Gln192Arg PON1 polymorphisms in 712 patients (437 Caucasian- and 275 African-Brazilians) who underwent coronary angiography. RESULTS: Among Caucasian-Brazilians, the homozygous 55LeuLeu frequency was higher among patients with significant coronary artery disease (CAD, obstructive lesions >/=50%) than among lesion-free controls (51% vs. 30.3%; p=0.022) in females, but not in males. The Gln192Arg PON1 polymorphism was not associated with CAD, although 192GlnGln homozygotes presented lower high-density lipoprotein (HDL)-cholesterol (p=0.035) and higher triglyceride (p=0.012) levels than 192Arg allele carriers among Caucasian-Brazilian males, but not females. No other lipid-genotype association was detected. Multivariate logistic regression corrected for classic CAD risk factors shows that 55LeuLeu PON1 homozygotes were at increased CAD risk (odds ratio OR=2.852; p=0.003) and that this genotype interacted with gender in its association with CAD risk (OR=0.290; p=0.006) among Caucasian-Brazilians. CONCLUSIONS: This report shows that the 55LeuLeu PON1 genotype increases CAD risk among female Caucasian-Brazilians, irrespective of other CAD risk factors. In addition, 192GlnGln PON1 homozygotes show higher triglyceride and lower HDL-cholesterol levels in male Caucasian-Brazilians. No associations were detected among African-Brazilians.

Smoking-dependent and haplotype-specific effects of endothelial nitric oxide synthase gene polymorphisms on angiographically assessed coronary artery disease in Caucasian- and African-Brazilians.

The nitric oxide produced by endothelial nitric oxide synthase (eNOS) plays a pivotal role in protecting the arterial wall from damages and atherosclerosis. The T-786C, the 27-bp repeat in intron 4, and the E298D eNOS gene polymorphisms were studied in 715 Brazilian patients (447 Caucasian- and 268 African-Brazilians) who underwent coronary angiography. The -786C frequency was increased in coronary artery disease (CAD) cases with significant lesions (> or =50% luminal obstruction) when compared with lesion-free controls; this difference was detected in smokers but not in nonsmokers, both in Caucasian- (p=0.011) and African-Brazilians (p=0.005). The interaction between -786C carriers and smoking was an independent CAD predictor (OR: 2.9, 95% CI: 1.4-5.9; p=0.003) in multiple logistic regression. The 298D mutation frequency was also higher among CAD cases (p=0.036) in African-Brazilian smokers, but this effect was not independent from other variables in the regression model. Though not associated with CAD, the 4-repeat allele combined with different T-786C alleles showed protective and susceptible effects in Caucasian-Brazilian smokers. The -786C/4-repeat/298E haplotype frequency was higher (p=0.020), whereas -786T/4-repeat/298E was lower (p=0.023) in these cases. These results showed a smoking-dependent effect of the T-786C eNOS polymorphism on CAD in both Caucasian- and African-Brazilians. Additionally, the haplotype analysis revealed different eNOS haplotypes associated with protection and susceptibility to the disease.

Endothelial nitric oxide synthase and fractalkine chemokine receptor polymorphisms on angiographically assessed coronary atherosclerosis.

BACKGROUND: The CX3CR1 is a fractalkine chemokine receptor expressed by leukocytes attracting them to the arterial wall inflammation. The endothelial nitric oxide synthase (eNOS) produces nitric oxide that acts on the vascular wall and circulating blood cells, lessening the inflammatory atherogenic damage. We determined if -786T > C and E298D eNOS and 745G>A CX3CR1 variants were associated with CAD risk and/or severity in Southern Brazilians of European descent. METHODS: We investigated these polymorphisms in 358 patients who had undergone coronary angiography and 129 non-symptomatic controls by PCR followed by restriction analyses. RESULTS: The 745 G > A CX3CR1 variant was not associated with CAD in this sample. Patients with significant CAD (coronary stenosis >or = 75%) presented higher frequencies of the eNOS -786C, but not of 298D allele than those observed among patients in whom significant CAD was ruled out by angiography (control group 1, p = 0.022) and non-symptomatic controls (control group 2, p < 0.001). The eNOS haplotypes derived from these 2 sites revealed that the frequency of haplotypes carrying the -786C allele (-786C/298D and -786C/298E) was increased and of the wild haplotype (-786T/298E) was decreased in patients with significant CAD (p = 0.003). After controlling for other classical risk factors carriers of haplotypes containing the -786C allele were at increased CAD risk (-786C/298D, OR = 2.95, p = 0.007; and -786C/298E, OR = 2.41, p = 0.030). CONCLUSIONS: The -786T > C was the polymorphism associated with severe CAD in this study. Haplotype analyses can be extremely helpful in unraveling the influence of different markers within a gene.

Common variants in the lipoprotein lipase gene in Brazil: association with lipids and angiographically assessed coronary atherosclerosis.

Lipoprotein lipase is the rate-limiting enzyme in the lipolysis of plasma triglyceride-rich lipoproteins. We studied six variants (T-93G, D9N, N291S, PvuII, HindIII and S447X) in the lipoprotein lipase (LPL) gene in 309 non-diabetic patients with angiographically assessed coronary artery disease and in 197 controls in a southern Brazilian population of European descent. The HindIII H-allele was associated with lower triglycerides (p < 0.01) and higher high-density lipoprotein cholesterol (p = 0.03) levels, and the S447X mutation was associated with lower triglyceride levels (p < 0.01) in males, but not females. No other significant lipid associations were observed. Haplotypes were derived from these two sites (HindIII/S447X), and carriers of H-S and H-X haplotypes showed lower triglycerides (p < 0.01) and increased high-density lipoprotein cholesterol (p = 0.01) levels when compared to the H+S haplotype in males. In this gender, the H-X haplotype was associated with a protective effect (OR = 0.36, 95%CI = 0.13-0.97) for significant disease (> or = 60% of luminal coronary stenosis), even controlling for other classical risk factors.