Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population

<div><p>Background and Aims</p><p>Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population.</p><p>Methods</p><p>We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively.</p><p>Results</p><p>Two single nucleotide polymorphisms near <i>MC4R</i> and <i>GNPDA2</i> genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, <i>P</i> = 4.75×10⁻⁴; OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, <i>P</i> = 4.54×10⁻³). When body mass index and waist circumference were further adjusted, the association of <i>MC4R</i> with type 2 diabetes remained significant (<i>P</i> = 1.81×10⁻²) and that of <i>GNPDA2</i> was attenuated (<i>P</i> = 1.26×10⁻¹), suggesting the effect of the locus including <i>GNPDA2</i> on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within <i>BAT2</i> was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (<i>P</i> = 1.04×10⁻²). In addition, four single nucleotide polymorphisms (near or within <i>SEC16B</i>, <i>BDNF</i>, <i>MAF</i> and <i>PRL</i> genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all <i>P</i> values<0.05).</p><p>Conclusions</p><p>This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population.</p>