Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance

We genotyped six single nucleotide polymorphisms (SNPs) in APPL2 in 1,808 non-diabetic subjects. Overweight and obesity were defined by body mass index (BMI). Obesity-related anthropometric parameters were measured, including height, weight, waist circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated.We found significant evidence of association with overweight/obesity for rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, p = 0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, p = 0.031 for rs1107756). After adjusting multiple comparisons, only the effect of rs2272495 on overweight/obesity remained to be significant (empirical p = 0.043). Moreover, we investigated the effects of these SNPs on obesity-related quantitative traits in all participants. rs2272495 was associated with BMI (p = 0.015), waist circumference (p = 0.006), hip circumference (p = 0.025) as well as WHR (p = 0.047) under a recessive model. Similar associations were found for rs1107756 except for WHR.This study suggests that genetic variations in APPL2 are associated with overweight and obesity in Chinese population with normal glucose tolerance.In recent years, the worldwide prevalence of obesity has increased dramatically and has became a major global epidemic impacting on morbidity and mortality. According to data from World Health Organization (WHO), more than 1 billion adults are overweight worldwide and at least 300 million are clinically obese [1]. Although the developments of obesity are mainly attributed to environmental and behavioural factors such as a sedentary habit and overly rich nutrition, multiple genetic components do predispose to this disease, which is suggested by genome-wide association studies (GWAS) and genetic epidemiologic researches [2]. Up to now, GWAS have identified approximately 50 loci associated with obesity [3].Adaptor protein, phosphoty