Different susceptibility to insulin resistance and fatty liver depending on the combination of TNF-α C-857T and adiponectin G+276T gene polymorphisms in Japanese subjects with type 2 diabetes.
The C-857T promoter polymorphism of TNF-α gene is associated with obese type 2 diabetes, while the adiponectin G+276T gene polymorphism in intron 2 may influence the fat accumulation in the liver.  In this study, we examined effects of these polymorphisms on clinical markers of insulin resistance and fatty liver (a liver/spleen CT ratio < 0.9).  These polymorphisms were determined in 342 Japanese subjects with type 2 diabetes.  The liver/spleen CT ratio was lower in the subjects with the adiponectin +276G/G genotype than that in the subjects with the +276T allele (P < 0.05), indicating that fat accumulation in the liver is associated with the +276G/G genotype.  Multiple comparisons among the 4 combinations of each polymorphism of the TNF-α and adiponectin genes revealed a significant difference in the liver/spleen CT ratio (P < 0.05) among the 4 groups, indicating that the gene combinations influence the degree of fat accumulation in the liver.  The subjects carrying the TNF-α -857T allele (C/T or T/T genotype) and the adiponectin +276G/G genotype had greater risks for fatty liver and insulin resistance that was evaluated by higher levels of fasting insulin and homeostasis model assessment of insulin resistance, as compared with the other groups.  Therefore, Japanese subjects with the TNF-α -857T allele and the adiponectin +276G/G genotype may be more susceptible to insulin resistance and fatty liver.  The present study provides the evidence for the interaction between TNF-α and adiponectin genes in the insulin resistance and fatty liver in Japanese subjects with type 2 diabetes.
Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Mio
M
Ohara
Chihaya
C
Maesawa
Noriko
N
Takebe
Toru
T
Takahashi
Mitsuhiro
M
Yamashina
Mitsutaka
M
Ono
Mizue
M
Matsui
Takayoshi
T
Sasai
Hiroyuki
H
Honma
Kan
K
Nagasawa
Fumikado
F
Fujiwara
Takashi
T
Kajiwara
Haruhito
H
Taneichi
Kazuma
K
Takahashi
Jo
J
Satoh
D052242:Adiponectin / Q000235:genetics*; D000704:Analysis of Variance; D000886:Anthropometry; D001774:Blood Chemical Analysis; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005234:Fatty Liver / Q000150:complications / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D008099:Liver / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013154:Spleen / Q000033:anatomy & histology; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D052242:Adiponectin; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha