To investigate the association of single nucleotide polymorphism (SNP) rs4355801 near osteoprotegerin (OPG) gene and rs3736228 in low-density lipoprotein receptor-related protein 5 (LRP5) gene with metabolic phenotypes [body mass index (BMI), waist-hip ratio, glucose, total cholesterol (CHO), and triglyceride], we carried out a population-based association study in Uyghur population living in Xinjiang Uyghur Autonomous Region of China. We observed a significant higher level of BMI in AG/AA carriers than in GG carriers (P = 0.022) for rs4355801. Subjects with the AG/GG genotype significantly increased the risk of BMI related obesity than subjects with the AA genotype, with an odds ratio of 1.31 (95% CI 1.09-1.56, P = 0.005). The association remained significant after controlling for covariates of age and gender. In addition, we observed a significant higher level of CHO in CT/TT carriers than in CC carriers (P = 0.021) for rs3736228. Our observations provide the first evidence that rs4355801 near OPG gene may confer susceptibility to obesity. In addition, SNP rs3736228 in LPR5 gene may affects the level of CHO in Uyghur population.