Interleukin‐6 polymorphism (–634C/G) in the promotor region and the progression of diabetic nephropathy in Type 2 diabetes

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine produced by many different cell types, including glomerular mesangial cells. Recently, a novel C/G polymorphism at position -634 in the promotor region of the IL-6 gene has been reported. The aim of this study was to investigate whether the -634C/G polymorphism is associated with an increased risk for progression to diabetic nephropathy as well as elevated levels of IL-6 secretion by peripheral blood mononuclear cells. The frequency of the -634C/G polymorphism was determined in Japanese patients with Type 2 diabetes and either normoalbuminuria (n = 162), microalbuminuria (n = 138), or macroalbuminuria (n = 154) by polymerase chain reaction-restriction fragment length polymorphism analysis. The level of IL-6 secretion in relation to genotype was assessed in lipopolysaccharide or advanced glycation end products-stimulated IL-6 secretion by peripheral mononuclear cells. The frequency of the -634G/G genotype and -634*G allele was significantly increased in the patients with macroalbuminuria compared with patients with normoalbuminuria (genotype: chi2 = 6.787, Pc = 0.0368; allele: chi2 = 9.080, Pc = 0.0104). Stepwise multiple regression analysis in these patients showed that hypertension (F = 40.48) and IL-6-634 gene polymorphism (F = 5.48) were the relevant variables for the progression of Type 2 diabetic nephropathy. Analysis of the IL-6 secretion data revealed that individuals carrying the -634*G allele had a higher IL-6 secretion capacity than those without the *G allele (P < 0.05). These results suggest that the IL-6-634C/G polymorphism may be a possible genetic susceptibility factor for the progression of diabetic nephropathy.