在病例、对照以及极度不一致的姐妹对中，与极端肥胖相关的FTO基因单核苷酸多态性。
FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs.
作者信息
Price R Arlen, Li Wei-Dong, Zhao Hongyu
机构信息
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
BMC Med Genet. 2008 Jan 24;9:4. doi: 10.1186/1471-2350-9-4.
BACKGROUND
FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs) in FTO with body mass index (BMI) and obesity, particularly rs1421085, rs17817449, and rs9939609.
METHODS
We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI<25 kg/m2) and had never been overweight during their lifetimes.
RESULTS
We detected highly significant associations of obesity with alleles in all three SNPs (p < 10-9). The strongest association was with rs1421085 (p = 3.04 x 10-10, OR = 1.75, CI = 1.47-2.08). A subset of 99 cases had extremely discordant sisters with BMI<25 kg/m2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 x 10-4).
CONCLUSION
These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.
背景
FTO是位于16号染色体区域12.2的一个基因。最近两项研究发现FTO基因中的几个单核苷酸多态性（SNP）与体重指数（BMI）及肥胖有关，尤其是rs1421085、rs17817449和rs9939609。
方法
我们检测了583名极度肥胖女性（当前BMI大于35kg/m2且终生BMI大于40kg/m2）及544名对照者（当前体重正常，BMI<25kg/m2且终生未超重）的这三个SNP。
结果
我们检测到所有三个SNP的等位基因与肥胖均有高度显著的关联（p<10-9）。最强的关联是与rs1421085（p = 3.04×10-10，OR = 1.75，CI = 1.47 - 2.08）。99例患者中有一部分有BMI<25kg/m2的姐妹，她们的BMI差异极大。这些姐妹在等位基因和基因型频率上的差异与总体病例和对照样本一致。最强的关联是与rs17817449（z = 3.57，p = 3.6×10-4）。
结论
这些结果表明FTO基因的常见变异与肥胖风险增加或抵抗有关，可能部分解释了密切相关个体之间的差异。
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