Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School, Providence, RI, USA.
Int J Obes (Lond). 2013 Dec;37(12):1545-52. doi: 10.1038/ijo.2013.54. Epub 2013 Apr 3.
Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss.
Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1.
No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56 kg per risk allele, P=0.005), but not ILI (P=0.761), resulting in SNP × treatment arm interaction (P=0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773 kg per risk allele), although results were of borderline statistical significance (P=0.051).
Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss.
全基因组关联研究为导致肥胖的遗传因素提供了新的见解。我们假设这些遗传标记也可以预测初始体重减轻后的体重减轻和体重反弹幅度。
在来自 Look AHEAD（糖尿病中的健康行动）的 3899 名超重或肥胖 2 型糖尿病患者中，对可在 Illumina CARe iSelect（IBC）芯片上获得的既定肥胖风险等位基因进行了特征描述，这是一项随机试验，旨在确定强化生活方式干预（ILI）和糖尿病支持和教育（DSE）对心血管发病率和死亡率的影响。主要分析检查了 8 个基因中 13 个肥胖风险多态性与随机治疗组之间的相互作用，以预测在第 1 年体重变化，以及在第 1 年通过基线体重减轻 3%或更多的个体中在第 4 年体重反弹。
没有单个核苷酸多态性（SNP）与体重减轻幅度或与第 1 年的治疗组显著相关。然而，脂肪量和肥胖相关基因（FTO）rs3751812 预测了 DSE 内的体重反弹（每个风险等位基因 1.56 公斤，P=0.005），但 ILI 没有（P=0.761），导致 SNP×治疗组相互作用（P=0.009）。在对先前研究的部分复制中，BDNF rs6265 处的肥胖风险（G）等位基因与治疗组之间的体重反弹更大（每个风险等位基因 0.773 公斤），尽管结果具有边缘统计学意义（P=0.051）。
FTO 和 BDNF 基因座的变异可能会增加减肥后的体重反弹风险。
