Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Int J Obes (Lond). 2011 May;35(5):676-83. doi: 10.1038/ijo.2010.166. Epub 2010 Aug 24.
To test whether DNA sequence variation in 11 obesity genes is associated with maximum weight loss and weight regain over 6 years of follow-up in bariatric surgery patients of the Swedish obese subjects (SOS) intervention study.
A total of 1443 subjects were available for analysis (vertical banded gastroplasty: n = 966, banding: n = 293 and gastric bypass: n = 184). Single-nucleotide polymorphisms (SNPs) from the following 11 genes were included: ADIPOQ, BDNF, FTO, GNB3, LEP, LEPR, MC4R, NR3C1, PPARG, PPARGC1A and TNF. General linear models were used to analyze associations between the SNPs and maximum weight loss and weight regain.
The average maximum weight loss was 33.7 kg (s.d. 13.3; min -95.5 kg, max +2.0 kg), which was reached 2.2 (s.d. 1.6) years after the surgery. Subjects regained approximately 12 kg (range 0.0-51.4 kg) by year 6. After correcting for multiple testing, the FTO SNP rs16945088 remained significantly associated with maximum weight loss (P = 0.0002), as minor allele carriers lost approximately 3 kg less compared with common allele homozygotes. This association was particularly evident in the banding surgery patients (P < 0.0001), whereas no significant association was found in the gastric bypass subjects. No other SNPs were associated with maximum weight loss. Furthermore, no SNPs were significantly associated with weight regain.
The FTO SNP rs16945088 was associated with maximum weight loss after banding surgery. We found no evidence that obesity-risk SNPs in FTO or other obesity candidate genes derived from genome-wide association studies are associated with maximum weight loss or weight regain over 6 years of follow-up in bariatric surgery patients. The potential role of other obesity genes remains to be investigated.
检测肥胖基因 11 个基因中的 DNA 序列变异是否与减肥手术患者随访 6 年期间的最大减重和体重反弹有关。
共对 1443 例患者进行分析（垂直束带胃成形术：n=966 例，束带术：n=293 例，胃旁路术：n=184 例）。纳入以下 11 个基因的单核苷酸多态性（SNP）：ADIPOQ、BDNF、FTO、GNB3、LEP、LEPR、MC4R、NR3C1、PPARG、PPARGC1A 和 TNF。采用线性回归模型分析 SNP 与最大减重和体重反弹的关系。
平均最大减重为 33.7kg（标准差 13.3kg；最小值-95.5kg，最大值+2.0kg），术后 2.2 年（标准差 1.6 年）达到减重高峰。随访 6 年后，患者体重反弹约 12kg（0.0-51.4kg）。经过多重检验校正后，FTO 基因 SNP rs16945088 与最大减重仍显著相关（P=0.0002），携带该 SNP 少数等位基因的患者比常见等位基因纯合子患者的减重少约 3kg。这种相关性在束带手术患者中尤为明显（P<0.0001），而在胃旁路手术患者中则无显著相关性。其他 SNP 与最大减重均无显著相关性。此外，没有 SNP 与体重反弹显著相关。
FTO 基因 SNP rs16945088 与束带手术后的最大减重相关。我们没有发现来自全基因组关联研究的 FTO 或其他肥胖候选基因中的肥胖风险 SNP 与减肥手术后 6 年的最大减重或体重反弹相关。其他肥胖基因的潜在作用仍有待研究。
