Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

APOA5 and APOA1 polymorphisms are associated with triglyceride levels in Mexican children.

BACKGROUND: Dyslipidemia is an important risk factor for the development of several diseases. The genetic component of hypertriglyceridemia has been studied in adults, but little is known in children. OBJECTIVE: The objective is to evaluate the association of two variants in APOA5 (rs662799) and APOA1 (rs5072) with triglyceride (TG) levels in Mexican children. METHODS: Anthropometric parameters were measured in 1559 Mexican children 5-14 years of age. DNA was isolated from blood samples. Lipid profiles and glucose concentrations were determined from serum and genotyping of rs662799, and rs5072 was performed using TaqMan® technology. Additive and dominant models adjusted for age, gender and body mass index were used to evaluate the association of these single nucleotide polymorphisms with TG levels. RESULTS: Children with high TG levels were found to have a higher body mass index and waist circumference as well as a worse lipids profile and glucose levels (p < 0.001). Additive and dominant models demonstrated a significant association between the rs662799 and rs5072 with TG. The dominant model showed the strongest significant association (OR = 1.81; 95% CI 1.46-2.24; p = 5.40 × 10-08 for rs662799 and OR = 1.54; 95% CI 1.05-2.25; p = 2.60 × 10-02 for rs5072). CONCLUSION: The minor alleles of rs662799 (APOA5) and rs5072 (APOA1) modulate TG levels in Mexican children.