Xu Ling, Zhang Fan, Zhang Dan-dan, Chen Xing-dong, Lu Ming, Lin Ren-yong, Wen Hao, Jin Li, Wang Xiao-feng
1MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Obesity (Silver Spring). 2009 Jan;17(1):121-5. doi: 10.1038/oby.2008.504. Epub 2008 Nov 13.
To test the hypothesis that micro-opioid receptor (OPRM1) gene might be involved in the prevalence of obesity, a population-based association study was carried out in Uyghur population. Overall 10 tagging single-nucleotide polymorphisms (tSNPs) in OPRM1 gene were genotyped. We showed that genotypes of rs1799971 in exon 1, and rs514980 and rs7773995 in intron 1 were significantly associated with the BMI. The BMI significantly decreased by the copy of minor allele carriers of rs1799971 which is a nonsynonymous functional polymorphism, whereas the BMI significantly increased by the copy of minor allele carriers of rs514980 and rs7773995. Subsequently, subjects were subsequently divided into case (BMI >or= 28) and control group (BMI < 24). Significant associations were again observed at rs1799971, rs514980, and rs7773995, regardless of controlling for covariates age and gender or not. The stronger evidence for association was found under the additive model for each of the three SNPs. The per-allele odds ratio of the minor allele for obesity was 0.75 (95% confidence interval 0.58-0.96, P = 0.023) for rs1799971, 1.68 (95% confidence interval 1.14-2.49, P = 0.009) for rs514980, and 1.80 (95% confidence interval 1.14-2.85, P = 0.012) for rs7773995, respectively. Our observations give the evidence that OPRM1 gene is involved in the prevalence of obesity in Uyghurs.
为了验证微阿片受体（OPRM1）基因可能与肥胖患病率有关这一假设，在维吾尔族人群中开展了一项基于人群的关联研究。对OPRM1基因中的10个标签单核苷酸多态性（tSNP）进行了基因分型。我们发现，外显子1中的rs1799971以及内含子1中的rs514980和rs7773995的基因型与体重指数（BMI）显著相关。rs1799971是一个非同义功能性多态性位点，其携带次要等位基因的拷贝会使BMI显著降低，而rs514980和rs7773995携带次要等位基因的拷贝则会使BMI显著升高。随后，将研究对象分为病例组（BMI≥28）和对照组（BMI＜24）。无论是否对年龄和性别等协变量进行控制，在rs1799971、rs514980和rs7773995位点均再次观察到显著关联。在这三个单核苷酸多态性位点的每一个位点上，在加性模型下发现了更强的关联证据。rs1799971肥胖的次要等位基因的每个等位基因优势比为0.75（95%置信区间0.58 - 0.96，P = 0.023），rs514980为1.68（95%置信区间1.14 - 2.49，P = 0.009），rs7773995为1.80（95%置信区间1.14 - 2.85，P = 0.012）。我们观察结果表明，OPRM1基因与维吾尔族人群肥胖患病率有关。
