Association Of The Interleukin-6 Receptor Gene Polymorphism With Metabolic Syndrome

Association of the interleukin-6 receptor gene polymorphism with metabolic syndromeBackgroundThe molecular etiology of metabolic syndrome (MS) remains unknown, but studies have clearly demonstrated that obesity, adipocyte-derived cytokine and inflammation have played important roles in the etiology of the disease. IL-6 play a central role in the developing of MS.IL-6 exerts its effects by binding to the IL-6 receptor (IL-6R). The IL-6R gene is located on chromosome 1q21 where have be reported linkage to obesity, T2DM and MS. Therefore, the IL-6R gene may be a worthwhile candidate gene to study these diseases.MS is a polygenic complex disorders showing the heterogeneity of phenotype, So we performed a critical case-control study for detecting the susceptibility genes.Objective(1) To examine the relationship between genetic variants in the IL6R gene and obesity, T2DM, MS in the Han nationality. (2) Analysis of the correlation between WC or BMI and IR indexes.MethodsWe identified 3 functional single nucleotide polymorphisms (SNPs) in the IL-6R gene: a Asp→Ala substitution at position 358 (rs8192284 A/C), a variant in the promoter -183 region (rs4845617 A/G), a variant in intron (rs8192283 A/T). The study population consisted 7456 subjects of the Han nationality from Dong-cheng district of Beijing, the case and control subjects were determined on different purposes.Results(1) The rs8197283 was no polymorphism in the 100 genotyped subjects; The rs4845617 and rs8192284 were in linkage disequilibrium(D'=0.61χ2=52.8 P＜0.05), About 1407 subjects were genotyped for rsS192284; (2) compared between obesity group (452 subgects) and control group (464 subjects), The carriers of Asp358 homozygotes had higher risk in developing obesity when compared with Ala 358 homozygotes. OR=1.32 (1.07-1.68), P=0.041;(3) The genotype distribution and allele frequency had no difference in T2DM group (198 subjects) and control group (306 subjects);(4) 1127 subjects were divided into Asp/Asp group, Asp/Ala group and Ala/Ala group for association study between Asp 358 Ala (rs8192284) polymorphism with metabolic syndrome, among the 3 groups, BMI, WC, FINS, 2hINS, ISI and prevalence of MS were different significantly. The prevalence of MS in the 3 groups was 22.8%, 16.9%, 11.1%, respectively, P=0.02;(5) WC and BMI correlated with 5 types of IR indexes significantly (p＜0.05). Among these IR indexes, WC and BMI correlated with lgISI2 (Beta: -.581, -.592 respectively) most strongly. Among different status of glucose metabolic groups, the correlation between WC and different types of IR indexes was most strongly in DM group.Conclusions(1) IL-6R gene polymorphism was significantly associated with obesity and MS, but had no association with T2DM in the Han nationality.(2) WC and BMI correlated with IR indexes significantly, the correlation was most strongly between WC or BMI with lgISI2. The correlation between WC and IR was stronger than that of BMI and IR in NGT group.