Association Study Of NLRP3Gene Single Nucleotide Polymorphisms In Type2Diabetes

OBJECTIVESThe NLRP3inflammasome, which is involved in interleukin-1β activaion and secretion, palys an important role in obesity-induced inflammation and insulin resistance. This study was to verification the correlation of the serum interleukin-1β levels with type2diabetes, and to explore the relationship of NLRP3gene rs10754558and rs4612666sites single nucleotide polymorphisms (SNPs) with type2diabetes.METHODSClinical data and blood samples of431type2diabetic patients and243healthy control subjects were collected in Xiangya hospital. Serum interleukin-ip levels were measured by ELISA, and NLRP3gene rs10754558(C/G) and rs4612666(C/T) sites single nucleotide polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Serum IL-1β concentration and the distribution frequency of NLRP3gene single nucleotide polymorphisms were compared between T2DM patients and healthy control subjects.RESULTS(1) Compared to healthy control subjects, serum IL-1β levels in type2diabetic patients increased significantly (P<0.01), and showed a positive correlation with the HOMA-IR and LDL-C (P<0.05) (2) The CC, CG, GG genotype frequencies of NLRP3gene rs10754558(C/G) in T2DM patients and healthy controls were31.8%,48.7%,19.5%and35.4%,53.5%,11.1%respectively, the C, G allelic frequencies in T2DM patients and healthy controls were56.1%,43.9%and62.1%,37.9%, respectively. The genotype and allelic frequencies of rs10754558(C/G) in T2DM patients were significantly different from those in healthy controls (P<0.05). Also we found that those who carried G allele in rs10754558(C/G) were associated with an increased risk of type2diabetes (OR=2.054,95%CI:1.601-2.636, P<0.01), and the CG/GG genotype of rs10754558polymorphism showed a significant association with a1.873fold increased risk of type2diabetes (95%CI:1.543-2.273,P<0.01).(3) The CC, CT, TT genotype frequencies of NLRP3gene rs4612666(C/T) inT2DM patients and healthy controls were23.2%,57.8%,19.0%and23.0%,50.6%,26.4%respectively, the C, T allelic frequencies in T2DM patients and healthy controls were52.1%,47.9%and48.4%,51.6%, respectively. There was no significant difference in the distribution of NLRP3gene rs4612666(C/T) polymorphisms genotypes and the two allelic forms, when type2diabetic patients were compared with the healthy control group (P>0.05)CONCLUSIONS(1) Levels of serum IL-1β are significantly increased in type2 diabetic patients. It suggests that chronic inflammation is related to type2diabetes.(2) NLRP3gene rs10754558polymorphisms is associated with risk of type2diabetes. Those who carried G allele or CG/GG genotypes in NLRP3gene rs10754558(C/G) are associated with an increased risk of type2diabetes.