Association Of The NLRP3Gene Single Nucleotide Polymorphisms With Metabolic Syndrome In Hunan Chinese Han People

Objective:The metabolic syndrome (MetS), composed of obesity, hypertension, hyperglycemia and dyslipidemia. Chronic low-grade systemic inflammation and insulin resistance play an important role in the development of metabolic syndrome. NLRP3, a member of nucleotide-binding oligomerization domain-like (NLR) family, has been recognized recently to play a pivotal role in obesity-induced inflammation and insulin resistance. And studies demonstrated that NLRP3gene single nucleotide polymorphisms (SNPs) may affect the NLRP3mRNA expression and its stability. Therefore, we hypothesized that the variants in NLRP3gene may contribute to MetS susceptibility. The aim of present study was to explore the association of NLRP3gene SNPs and metabolic syndrome in Huan Chinese Han people.Methods:The study consisted of760subjects including410MetS patients and350normal controls. All the participants were unrelated Chinese Hans from Hunan province. MetS was defined according to the International Diabetes Federation (IDF) criteria, and the cutoff values for waist circumference were90cm for men and85cm for women, respectively. Two common SNPs of NLRP3gene, rs10754558and rs4612666,were detected using the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method. Genotype and allele frequencies were compared between MetS patients and normal controls. And clinical characteristics were compared among subjects with different genotypes of rs10754558.Results:1. Genotype frequencies of rs10754558and rs4612666were in Hardy-Weinberg equilibrium for both control groups (P=0.802, P=0.389, respectively).2. The frequencies of rs10754558genotypes GG, GC and CC were24%,41.6%,34.4%in the MetS group and11.4%,48%,40.6%in the control group, respectively. The frequencies of allele G and C were44.8%,55.2%in the MetS group and35.4%,64.6%in the control group, respectively. The frequencies of rs4612666genotypes TT, TC and CC were31.5%,41.2%,27.3%in the MetS group and32.9%,44.3%,22.8%in the control group, respectively. The frequencies of allele T and C were52.1%,47.9%in the MetS group and55%,45%in the control group, respectively. There were significant differences in frequencies of the genotype and allele in rs10754558polymorphism between normal control and MetS patients (P<0.001, P<0.001, respectively). While the genotype and allele frequencies of rs4612666were not significant different between the control and MetS group.3. The OR for those with genotype GG compared with those with genotype CC of rs10754558was2.467after adjustments for age, sex (OR=2.467;95%CI,1.596-3.813; p=0.000).4. Clinical characteristics were compared among subjects with different rs10754558genotypes. Lever of HOMA-IR in MetS patients with GG genotype was significantly higher than those with CC genotype (P=0.019).Conclusions:1. NLRP3gene rs10754558variants confer increased risk of MetS in Hunan Chinese Han population. The G allele and genotype GG are risk factors of MetS.2. NLRP3rs10754558GG genotype is associated with higher level of insulin resistance.3. NLRP3rs4612666SNPs are not related to MetS susceptibility in this population.