Amerindians show no association of PC-1 gene Gln121 allele and obesity: a thrifty gene population genetics
BACKGROUND Obesity is considered to be a multifactorial trait resulting from the combined influence of genetic and environmental determinants. Insulin resistance plays an important role in the development of obesity. Plasma-cell membrane differentiation antigene-1 (PC-1) inhibits insulin receptor signalling when overexpressed and thus causes insulin resistance. PC-1 gene polymorphism might be associated with adipocyte metabolism disturbance and energy imbalance. The purpose of this study was to determine whether K121Q polymorphism in PC-1 gene is involved in obesity susceptibility in Chinese Han population. METHODS The genotype of the polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism analysis for 338 unrelated subjects of Beijing, China. Their Body mass index (BMI), plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), free fatty acid (FFA) and insulin level were measured. Chi-square analyses were applied to test the significance differences in genotypic and allelic frequencies. Association studies were undertaken using the t-test and logistic regression analyses. RESULTS The obese had significantly higher frequency of KQ/QQ genotype or Q allele than non-obese in females (26.7% vs. 10.9%, p = 0.014 and 13.3% vs. 5.5%, p = 0.021). Significant elevation of insulin amongst the Q121 carrier women in obesity individuals and higher FFA level of Q121 carrier men in non-obese controls (BMI < or = 23 kg/m2) were observed. Binary logistic regression analysis revealed that PC-1 genotype together with higher glucose, total cholesterol, triglyceride and serum HDL were independently associated with the presence of obesity. CONCLUSIONS The observed genotype distributions revealed a significant association of PC-1 K121Q with obesity. PC-1 Q121 carriers are more likely to be insulin-resistant or get fatter in respect to KK subjects and carriers of the Q allele are at higher risk for the development of obesity in female.