Variants of NLRP3 gene are associated with insulin resistance in Chinese Han population with type-2 diabetes

Abstract

Aims: Nod like receptor pyrin domain containing 3 (NLRP3) is the best characterized member of nod like receptor family. Recent studies suggest that NLRP3 plays a crucial role in the pathogenesis of type-2 diabetes (T2DM), and variants in NLRP3 affect its mRNA stability and expression. Therefore, we hypothesize that the variants in NLRP3 gene may contribute to T2DM susceptibility. The aim of this study is to evaluate the association of NLRP3 SNPs with T2DM in Chinese Han patients.

Methods: Two common variants in NLRP3 gene, rs10754558 and rs4612666, were detected using the polymerase chain reaction-restriction fragment length polymorphism procedure in 952 unrelated T2DM patients and 871 healthy controls. All participants were unrelated Chinese Hans.

Results: The GG genotype and G allele frequencies of rs10754558 were significantly higher in T2DM patients than those in controls (for GG genotype, 19.6% vs. 14.5%, p=0.019; for G allele, 43.9% vs. 39.8%, p=0.013). The GG genotype of rs10754558 was significantly associated with higher LDL-C levels and more prone to insulin resistance, as evaluated by HOMA-IR or QUICK indexes.

Conclusions: The variant (rs10754558) in NLRP3 is related to insulin resistance and increased risk of T2DM in Chinese Han population.

Keywords: ASC; CI; GWAS; Gene polymorphisms; HDL-C; HDL-cholesterol; HOMA; IR; Insulin resistance; LDL-C; LDL-cholesterol; NLRP3; OR; PCR–RFLP; QUICK; T2DM; Type-2 diabetes; apoptosis-associated speck-like protein containing a caspase recruitment domain; confidential interval; genome-wide association studies; homeostasis model assessment; insulin resistance; nod like receptor pyrin domain containing 3; odds ratio; polymerase chain reaction–restriction fragment length polymorphism; quantitative insulin sensitivity check index; type-2 diabetes.