Tohoku J. Exp. Med., 2012, 226(2)

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

MIO OHARA,¹ CHIHAYA MAESAWA,² NORIKO TAKEBE,¹ TORU TAKAHASHI,¹ MITSUHIRO YAMASHINA,¹ MITSUTAKA ONO,¹ MIZUE MATSUI,¹ TAKAYOSHI SASAI,¹ HIROYUKI HONMA,¹ KAN NAGASAWA,¹ FUMIKADO FUJIWARA,¹ TAKASHI KAJIWARA,¹ HARUHITO TANEICHI,¹ KAZUMA TAKAHASHI¹ and JO SATOH¹

¹Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
²Division of Bioscience, Department of Tumor Biology, Center for Advanced Medical Science, Iwate Medical University School of Medicine, Morioka, Japan

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.

keywords —— adiponectin; fatty liver; gene polymorphism; insulin resistance; TNF-α

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 226, 161-169

Correspondence: Jo Satoh, Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University, School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan

e-mail: jsatoh@iwate-med.ac.jp