Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.
High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.
Kubaszek
Agata
A
Department of Medicine, University of Kuopio, Kuopio, Finland.
Pihlajamäki
Jussi
J
Komarovski
Vladislav
V
Lindi
Virpi
V
Lindström
Jaana
J
Eriksson
Johan
J
Valle
Timo T
TT
Hämäläinen
Helena
H
Ilanne-Parikka
Pirjo
P
Keinänen-Kiukaanniemi
Sirkka
S
Tuomilehto
Jaakko
J
Uusitupa
Matti
M
Laakso
Markku
M
D000704:Analysis of Variance; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha