Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
These results suggest that the IL-6-634C/G polymorphism may be a possible genetic susceptibility factor for the progression of diabetic nephropathy.
Kitamura
A
A
The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Hasegawa
G
G
Obayashi
H
H
Kamiuchi
K
K
Ishii
M
M
Yano
M
M
Tanaka
T
T
Yamaguchi
M
M
Shigeta
H
H
Ogata
M
M
Nakamura
N
N
Yoshikawa
T
T
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D015850:Interleukin-6