Gender Differences in the Relationship of ENPP1/PC‐1 Variants to Obesity in a Turkish Population

Abstract

The ectoenzyme ENPP1 (also termed membrane glycoprotein PC-1 or ENPP1/PC-1) is an inhibitor of insulin-induced activation of the insulin receptor. There is evidence from previous studies that coding variants of ENPP1/PC-1 (K121Q) are associated with type 2 diabetes (T2D) and obesity. Studies in the general Turkish population have demonstrated: unique plasma lipid characteristics; a high prevalence of cardiovascular risk factors; and an increased prevalence of obesity and T2D. We investigated, therefore, the association of ENPP1/PC-1 variants with obesity and T2D in Turkish individuals. The TaqMan allelic discrimination assay was used for genotyping the relationship of ENPP1/PC-1 variants to obesity and T2D in a genetic association study of 1553 genotyped, randomly selected subjects from the Turkish Heart Study. The K121Q (rs1044498) variant, and other previously reported variants (rs997509, rs1799774, rs1044548, rs11964389, rs7754561) were analyzed. In this cohort, the minor allele frequency of the K121Q variant was associated with obesity in male, but not female, subjects (male, OR 1.64, CI%95 1.004-2.698, p = 0.048; female, OR 1.003, CI%95 0.684-1.471, p=ns.). In addition, the previously reported ENPP1/PC-1 “risk haplotype” [Q (rs1044498), delT (rs1799774), and G (rs7754561) alleles] was found to be associated with obesity in male, but not female, subjects (p = 0.035). In contrast, there was no association of either the K121Q variant or the ENPP1/PC-1 haplotype with T2D. We find evidence that variants of ENPP1/PC-1 are associated with obesity in the male Turkish population and thus these variants may contribute to the development of the obesity in these individuals.

Genetics in Arterial Calcification

“…A noteworthy confounder is that ENPP1 variants differentially modulate insulin receptor signaling 157 and K173Q and other SNPs in ENPP1 may have an indirect effect on parameters affecting arterial calcification in certain populations.…”

Insulin signaling regulating genes: effect on T2DM and cardiovascular risk

“…Similar data have been reported for TCF7L2, which is 84 insulin resistance prospectively predicts decreased BMI. 85 Accordingly, several genetic variants that predict increased insulin sensitivity are associated with increased BMI, whereas genetic variants that are associated with insulin resistance are also associated with reduced BMI. 4 In vitro studies suggest a direct effect of the Q121 variant of ENPP1 on adipogenesis.…”

Genetic Variants of theENPP1/PC-1Gene Are Associated With Hypertriglyceridemia in Male Subjects

“…We found that both the Q121 variant and the "at risk" haplotype were associated with obesity in males but not in females. 30 Wan et al reported a gender difference in the association between the Q121 variant and the risk of obesity in a Chinese population. 29 In contrast to our previous study, 30 they found that female subjects with the Q allele were at higher risk for obesity than males.…”

“…30 Wan et al reported a gender difference in the association between the Q121 variant and the risk of obesity in a Chinese population. 29 In contrast to our previous study, 30 they found that female subjects with the Q allele were at higher risk for obesity than males. We did not fi nd any gender-SNP(s) interaction on TG levels in the present study.…”