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Objective: Published data concerning associations between 1RS1 variants and type 2 diabetes and related traits have been inconsistent. We examined the relationship between common variants in IRS1, type 2 diabetes, and related traits including insulin resistance, hyperglycemia and DNA damage in the Boston Puerto Rican Health Study. Methods: We genotyped six common 1RS1 variants in an adult Puerto Rican population (n=1132) and tested for association with risk of type 2 diabetes and related traits. Results: SNPs rs934167 and rs 1801123 showed significant association with fasting glucose concentrations (p = 0.005 and p = 0.016, respectively) and rs934167 showed significant association with plasma insulin levels (p = 0.005). Carriers of the rs934167 minor allele had significantly higher HOMA-IR and lower QUICKI (p = 0.001 andp = 0.001, respectively), and a 40% and 58% greater likelihood of being hyperglycaemic or hyperinsulinemic (OR = 1.40 and 1.58; p = 0.013 and 0.002, respectively). However, they exhibited only a marginally significant trend towards having type 2 diabetes (OR=1.27, p = 0.077). Furthermore, carriers of the haplotype C-T of the rs934167 and rsl801123 minor alleles showed consistent patterns of associations after correction for multiple testing. In addition, the G972R (rs 1801278) minor allele was significantly associated with higher urinary 8-OHdG concentrations (p = 0.020) and plasma CRP levels (p = 0.035). Conclusions: Our results support 1RS1 variants associated with type 2 diabetes risk in adult Puerto Ricans. Moreover, we report the novel finding that IRS1 variant G972R (rs 1801278) may contribute to oxidative DNA damage and inflammation. [ABSTRACT FROM AUTHOR]

Although methylenetetrahydrofolate reductase (MTHFR) genetic variants are associated with plasma homocysteine lHcy) and cardiovascular disease (CVD), little is known whether dietary fatty acid intake modulates these associations. The goal was to examine the interaction of MTHFR variants with dietary fatty acids influencing plasma Hcy in 995 Boston Puerto Rican adults. We found that plasma Hcy concentration was negatively correlated with )n-3) PUFA intake (r= -0.117; P= 0.022), and the ratio of (n-3):(n-6) PUFA in the diet )r= -0.122; P= 0.009). Further, 2 functional MTHFRvariants, 1 298A>C and 677C>T, which are not in linkage disequilibrium in this population, were significantly associated with hypertension (OR F 1.72, P = 0.024, and OR = 1.60, P = 0.002, respectively). In addition, the 1298A>C variant was significantly associated with CVD (OR = 3.32; P = 0.030). Importantly, this variant exhibited significant interactions with intakes of total and )n-6) PUFA and the ln-3(:(n-6( PUFA ratio of the diet. The plasma Hcy concentration of carriers of risk allele 1 298C was greater than that of noncarriers only when participants had consumed a high-PUFA diet (>7.8% energy) but was not greater when they had low intake of PUFA (>7.8% energy). In addition, participants with combined genotypes of both SNP (677 with 1298 AC or CC) who consumed high levels of (n-3) PUFA (>0.66% energy) had lower plasma Hcy compared with those who had the same genotype and consumed low levels of (n-3) PUFA (<0.66% energy). Our study suggests that dietary PUFA intake modulates the effect of 2 MTHFR variants on plasma Hcy in Boston Puerto Rican adults. [ABSTRACT FROM AUTHOR]