Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong.
J Clin Endocrinol Metab. 2010 Mar;95(3):1395-403. doi: 10.1210/jc.2009-1465. Epub 2010 Jan 8.
Recent large-scale genome-wide association studies identified novel genetic variants associated with obesity and body mass index (BMI) in addition to the well-described FTO and MC4R genetic variants.
This study aimed to examine 13 previously reported obesity and/or BMI-associated loci for associations with obesity in Chinese.
This was a cross-sectional case-control study in 470 obese cases (BMI > or =27.5 kg/m(2)) and 700 normal-weight controls (18.5 < or = BMI < or = 23.0 kg/m(2)).
A significant association with obesity could be replicated (one tailed P < 0.05) in seven of the 13 single-nucleotide polymorphisms (SNPs) in the case-control study. These included GNPDA2 rs10938397 (P = 7.3 x 10(-4)); FTO rs8050136 (P = 8 x 10(-4)); MC4R rs17782313 (P = 1.2 x 10(-3)); KCTD15 rs29941 (P = 8 x 10(-3)); SFRS10-ETV5-DGKG rs7647305 (P = 0.023); SEC16B-RASAL2 rs10913469 (P = 0.041); and NEGR1 rs3101336 (P = 0.046). Combined genetic risk scores were calculated, and we observed ORs ranging from 1.17 to 1.23 for each unit increase in the genetic risk scores. Associations with obesity-related quantitative traits were analyzed separately for cases and controls. KCTD15 SNP rs29941 (P = 1 x 10(-3)) was significantly associated with fasting glucose in the control group, whereas only the FTO SNP rs8050136 was associated with BMI (P = 3.5 x 10(-3)) in the obese group. However, in an extension study of 1938 subjects from the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, rs8050136, rs10938397, and rs17782313 showed significant associations with BMI.
We have succeeded in replicating, in a Chinese population, the associations with obesity in seven SNPs reported in recent genome-wide association studies. Further functional and fine-mapping studies to elucidate the roles of these putative obesity-related genes and genetic variants are warranted.
最近的大规模全基因组关联研究发现了除了已知的 FTO 和 MC4R 基因变异以外，与肥胖和体重指数（BMI）相关的新的遗传变异。
本研究旨在检测 13 个已报道的肥胖和/或 BMI 相关基因座，以研究其与中国人肥胖的关系。
这是一项在中国肥胖病例（BMI≥27.5kg/m2）470 例和正常体重对照组（18.5≤BMI≤23.0kg/m2）700 例的横断面病例对照研究。
在病例对照研究中，13 个单核苷酸多态性（SNP）中有 7 个与肥胖显著相关（单侧 P＜0.05）。这些 SNP 包括 GNPDA2 rs10938397（P=7.3×10-4）；FTO rs8050136（P=8×10-4）；MC4R rs17782313（P=1.2×10-3）；KCTD15 rs29941（P=8×10-3）；SFRS10-ETV5-DGKG rs7647305（P=0.023）；SEC16B-RASAL2 rs10913469（P=0.041）；和 NEGR1 rs3101336（P=0.046）。我们计算了综合遗传风险评分，发现每个遗传风险评分单位增加时，OR 值在 1.17 到 1.23 之间。我们分别对病例组和对照组的肥胖相关定量特征进行了关联分析。KCTD15 SNP rs29941（P=1×10-3）在对照组中与空腹血糖显著相关，而只有 FTO SNP rs8050136与肥胖组的 BMI 相关（P=3.5×10-3）。然而，在香港心血管危险因素患病率研究的一个基于人群的 1938 例扩展研究中，rs8050136、rs10938397 和 rs17782313 与 BMI 呈显著相关。
我们成功地在中国人群中复制了最近全基因组关联研究中与肥胖相关的 7 个 SNP 的关联。需要进一步的功能和精细映射研究来阐明这些假定的肥胖相关基因和遗传变异的作用。
