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Variants of NLRP3 gene are associated with insulin resistance in Chinese Han population with type-2 diabetes
Authors:Yingying Zheng  Dongmei Zhang  Li Zhang  Mao Fu  Yi Zeng  Ryan Russell
Institution:1. Department of Endocrinology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, China;2. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA
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:NLRP3  nod like receptor pyrin domain containing 3  T2DM  type-2 diabetes  ASC  apoptosis-associated speck-like protein containing a caspase recruitment domain  IR  insulin resistance  GWAS  genome-wide association studies  HDL-C  HDL-cholesterol  LDL-C  LDL-cholesterol  HOMA  homeostasis model assessment  QUICK  quantitative insulin sensitivity check index  PCR&ndash  RFLP  polymerase chain reaction&ndash  restriction fragment length polymorphism  OR  odds ratio  CI  confidential interval
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