Different Susceptibility to Insulin Resistance and Fatty Liver Depending on the Combination of TNF-.ALPHA. C-857T and Adiponectin G+276T Gene Polymorphisms in Japanese Subjects with Type 2 Diabetes

Abstract

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.

The -308G>A Polymorphism of the TNF Gene Is Associated With Proliferative Diabetic Retinopathy in Caucasian Brazilians With Type 2 Diabetes

“…10 The À308G>A polymorphism was associated with the progression of impaired glucose tolerance to type 2 diabetes in Finns, 11 type 2 diabetes in Asians, 12,13 macrovascular complications in Scandinavians, 14 and renal disease in Poles and Chinese with diabetes. 15,16 In the Japanese population, the À857C>T polymorphism was associated with insulin resistance, 17 type 2 diabetes, 18 and carotid plaque formation in subjects with type 2 diabetes. 19 Therefore, these findings prompted us to test the hypothesis that the À238G>A (rs361525), À308G>A (rs1800629), and À857C>T (rs1799724) polymorphisms in the TNF gene are associated with DR in Caucasian Brazilians with type 2 diabetes.…”

Tumor necrosis factor alpha gene rs1799724 polymorphism in Alzheimer’s disease

“…In Japanese population, -857C>T (rs1799724) polymorphism is associated with insulin resistance, T2DM, and carotid plaque formation in T2DM patients (Kamizono et al 2000;Buraczynska et al 2004;Wang et al 2005;Yamashina et al 2007;Ohara et al 2012). However, Sesti et al (2015) found an independent association of the 308G>A polymorphism in the TNFα gene with proliferative diabetic retinopathy PDR in Caucasian Brazilians with T2DM, not -857C>T (rs1799724) polymorphism.…”

Impact of Genetic Polymorphisms on Insulin Resistance

“…On the other hand, another recent meta-analyses has reported that TNF-α -238G>A and -308G>A polymorphisms were not associated with type 2 diabetes mellitus; however, -308G>A polymorphism was positively associated with type 1 diabetes (Feng et al, 2009a;Feng et al, 2009b;Feng et al, 2011). TNF-α -857C>T polymorphism is also associated with obese type 2 diabetes (Kamizono et al 2000) and insulin resistance in Japanese diabetic subjects with adiponectin +276GG genotype (Ohara et al, 2012). The study of Ohara et al has shown interaction of TNF-α and adiponectin genes with insulin resistance and fatty liver (Ohara et al, 2012).…”

“…TNF-α -857C>T polymorphism is also associated with obese type 2 diabetes (Kamizono et al 2000) and insulin resistance in Japanese diabetic subjects with adiponectin +276GG genotype (Ohara et al, 2012). The study of Ohara et al has shown interaction of TNF-α and adiponectin genes with insulin resistance and fatty liver (Ohara et al, 2012).…”