Association Of Polymorphism In The Interleukin-6 Gene With Diabetic Nephropathy In Type 2 Diabetes

Background and Objective Diabetic nephropathy (DN) is a major microangiopathy complication of diabetes mellitus (DM). The mechanism of the development of diabetic nephropathy is very complicated, which is associated with environmental factors as well as genetic factors. Interleukin-6(IL-6) is a multifunctional cytokine produced by many different cell types, including lymphocytes, endothelial cells, fibroblastes and glomerular cells. Recent investigations indicate that genetic variations in IL-6 maybe play a role in the pathogenesis of macroangiopathy and microangiopathy. This investigation is carried out to evaluate the association of IL-6 gene -634C/G polymorphism in the promoter region with diabetic nephropathy who are in Wuhan district of Hubei province.Methods 393 Hans in Wuhan district of Hubei province are recruited onto the study, including 267 cases of type 2 diabetes mellitus (90 with normoalbuminuria,85 with microalbuminuria and 92 with macroalbuminuria) and 126 the normal controls. IL-6 gene polymorphism is determined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing of the representative PCR products with variant patterns. The genotype frequencies and the allele frequencies are statistically compared among different groups.Result (1)When the target gene is cut by the restriction endonuclease BsrB I, there are three kinds of genotypes to appear, including GG (homozygous mutation), CG (heterozygous mutation) and CC (wide-type). At the same time, two kinds of alleles, C and G, are found in the study; (2)The frequencies of GG genotype and G allele were significantly increased in the patients with macroalbuminuria (1.9%,26.1% respectively) compared with the patients with normoalbuminuria(3.3%,13.3% respectively)and the control group(2.4%,15.1% respectively); (3)Compared with thepatients with normoalbuminuria and the control group, IL-6 genotype frequencies and allele frequencies in the patients with microalbuminuria did" not reach statistical significance (both P>0.05); (4)No significant differences in IL-6 genotype frequencies and allele frequencies were observed between type 2 diabetes mellitus and the control group (x2=2.42vP=0.120;x2=3.34,P=0.188); (5)There are no significant difference in clinical characteristics of type 2 diabetes mellitus among three kinds of genotypes of IL-6 gene (P>0.05) .Conclusion IL-6 gene -634C/G polymorphism in the promoter region is associated with progression of diabetic nephropathy in Chinese Hubei Hans patients with type 2 diabetes mellitus. The presence of G allele may represent a risk factor for diabetic nephropathy in type 2 diabetes mellitus.