Gender differences in the association of ENPP1 polymorphisms with type 2 diabetes in a Chinese population

Abstract Background Ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ) encodes the human plasma-cell membrane differentiation antigen-1, and ENPP1 variants have been shown to be associated with type 2 diabetes (T2D) and insulin resistance. In this study, we investigated the involvement of ENPP1 polymorphisms in T2D. Methods The association of the two polymorphisms of ENPP1 (rs7754586 and rs55725924) with T2D and diabetes-related quantitative traits was analyzed in Chinese samples containing 929 T2D patients and 1044 healthy individuals. We also performed the expression quantitative trait loci (eQTL) analysis to study the association of both polymorphisms of ENPP1 with mRNA expression levels using the genotype-tissue expression database. Results The risk allele A of the polymorphism rs7754586 contributed to T2D (odds ratio: 1.252, 95% confidence interval: 1.044–1.615, P  = 0.018). The polymorphism rs55725924 was associated with the diastolic blood pressure and cholesterol levels. Patients carrying high-risk haplotype A-T of rs7754586 and rs55725924 exhibited a high risk of acquiring T2D. These associations were only observed in males, but not in females. In addition, the eQTL analysis demonstrated that the risk allele of rs7754586 was associated with higher levels of ENPP1 mRNA expression. Conclusion Our findings suggest that the ENPP1 polymorphism rs7754586 may implicate in the pathogenesis of T2D in men, while polymorphism rs55725924 may be involved in diastolic blood pressure and cholesterol of male T2D patients.