NLRP3、TLR4基因多态性与TyG指数交互作用对痛风的影响

Impact of interaction between NLRP3,TLR4 gene polymorphisms and triglyceride-glucose index on gout

目的探讨三酰甘油葡萄糖(TyG)指数和Toll样受体4(Toll-like receptor 4,TLR4)、NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)基因单核苷酸多态性对痛风的危险性以及基因与TyG指数交互作用对痛风易感性的影响。方法选取男性痛风患者315例和同期健康男性体检者499名,通过问卷调查收集研究对象的一般信息,并采集其外周静脉血检测血液生化指标;采用多重连接酶检测反应对NLRP3、TLR4的3个单核苷酸多态性(SNP)位点进行检测,应用logistic回归分析比较NLRP3、TLR4等位基因与痛风风险之间的相关性;采用广义多因素降维法(GMDR)模型和logistic回归分型分析SNP与TyG指数与痛风的交互作用。结果对吸烟、饮酒等因素进行校正后TyG指数每增加1个标准差痛风的风险增加61.1%。rs10754558、rs10759932和rs7525979的CC基因型为汉族痛风高危险基因型。GMDR结果显示,rs10754558-TyG指数、rs7525979-TyG指数和rs10759932-TyG指数的交互作用模型在对照组和痛风组间的差异均存在统计学意义(P<0.05),提示所选取的3个SNP基因型与TyG指数之间可能存在交互作用。对所选取的3个SNP基因型与TyG指数进行分层分析,发现在校正年龄、吸烟等因素后,rs10754558位点携带C/C或C/G基因型的高TyG指数者相对携带GG基因型和低TyG指数者痛风风险增加(OR=2.127,P<0.05)。结论rs10754558、rs10759932和rs7525979的CC基因型为汉族痛风高危险基因型,rs10754558与TyG指数之间的相互作用可能增加痛风的发病风险。

Objective To explore the effect of triglyceride glucose(TyG)index,single nucleotide polymorphism of Toll-like receptor 4(TLR4)and NOD-like receptor thermal protein domain associated protein 3(NLRP3)genes,and its interaction on the risk of gout.Methods A total of 315 male patients with gout and 499 men for health checkup at the same period were selected.General data were collected through questionnaires,and peripheral venous blood was collected for biochemical test.Three single nucleotide polymorphisms(SNPs)of NLRP3 and TLR4 were detected with multiplex ligase assay reaction,and logistic regression analysis was applied to compare the correlation between NLRP3 and TLR4 alleles and gout risk.The interaction of SNP and TyG index with gout was analyzed by generalized multi-factor dimensionality reduction(GMDR)model and logistic regression.Results After adjusting for smoking,drinking,and other factors,the risk of gout increased by 61.1%for each standard deviation increase in TyG index.CC genotypes of rs10754558,rs10759932,and rs7525979 were high risk genotypes of gout in Han ethnicity.GMDR results showed significant differences in the interaction models of rs10754558-TyG index,rs7525979-TyG index,and rs10759932-TyG index between control group and gout group(P<0.05),suggesting an interaction between the three genotypes of SNPs selected and TyG index.Stratified analysis of the three selected SNPs and TyG index showed that after adjusting for age,smoking,and other factors,the high TyG index patients carrying C/C or C/G genotype at rs10754558 displayed an increased risk of gout compared with those carrying GG genotype and low TyG index(OR=2.127,P<0.05).Conclusion The CC genotypes of rs10754558,rs10759932,and rs7525979 are high risk genotypes for gout in Han ethnicity.The interaction between rs10754558 and TyG index may increase the risk of gout development.