Association Of Genetic Variants In Sirt1 And Nrf2 Gene With Metabolic Syndrome Risk In A Chinese Han Population

BackgroundMetabolic syndrome is a complex of interrelated risk factors including central adiposity,raised blood pressure,hyperglycemia,elevated triglyceride levels and low high-density lipoprotein.Sirtl gene has important effects on regulation of mammalian lifespan,gluconeogenesis and insulin secretion and so on.Nrf2 is a key regulator of antioxidant signaling that may prevent the development of metabolic syndrome.This study is aimed to investigate the association of metabolic syndrome and Sirtl gene and Nrf2 gene polymorphisms regarding rs2273773,rs7895833,rs6721961 in a Chinese Han population.MethodsOur study recruited 964 Chinese Han citizens from a community of Hangzhou City,Zhejiang Province in 2010.According to inclusion and exclusion criteria,690 participants(278 males and 412 females)were followed up at the end.The sample comprised 141 individuals with MetS based on Guidelines for the prevention and treatment of dyslipidemia in Chinese adults and 549 individuals without MetS.The research investigated the general information and measured the waist circumference,blood pressure,the serum level of low-density lipoprotein cholesterol,insulin and so on.? Genotyping of these polymorphisms(Sirtl rs2273773,Sirtl rs7895833 and Nrf2 rs6721961)was performed using polymerase chain reaction with confronting two-pair primers assay(PCR-CTPP).? We compared clinical data of MetS subjects with these of control group using the software of SPSS 22.0.The genotype distributions in MetS and non-Mets group were tested by binary regression method.We also analyzed the associations between gene polymorphisms and clinical materials.Results1.The body weight,BMI index,waist circumference,hip circumference,waist/hip ratio,blood pressure,HOMA-IR,the serum level of TC,TG,ALT,uric acid,urea nitrogen,?-GT significantly increased in patients as compared to control group(P<0.05)and the serum level of HDL-C significantly decreased(P<0.001)· There was no significant difference in other clinical data.2.The AA genotype of rs7895833 was 2.54 times higher in MetS than those of AG(P=0.004)and 1.91 times higher than those of GG(P=0.035).There was no significant difference between AG and GG groups(P=0.166).3.The serum level of low-density lipoprotein cholesterol,insulin and HOMA-IR were significantly higher(P<0.05)in AA genotype of rs7895833 compared with AG and GG genotype in general population.And the serum level of total cholesterol in AA genotype was lower(regression coefficient±SE:-0.117±0.055;P=0.033)than AG and GG genotype.4.However,the genotype frequency of Sirt1 rs2273773 and Nrf2 rs6721961 in MetS group were not significantly different from that in the control subjects.And those two genetic veriants were not correlated with metabolic traits.ConclusionsThe polymorphisms of Sirtl rs7895833 are associated with metabolic syndrome in a Chinese Han population.The risk for MetS was increased in carriers of AA.The serum level of LDL-C,insulin and HOMA-IR were significantly higher and the serum level of total cholesterol was significantly lower in AA group.