Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands,
Genes Nutr. 2014 Nov;9(6):434. doi: 10.1007/s12263-014-0434-2. Epub 2014 Oct 17.
Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % (>8 kg/10 year; n = 237). Starting BMI was between 20 and 35 kg/m(2) and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (χ (2) p = 0.005), ACE rs4340 (χ (2) p = 0.006) and AKR1C2 rs12249281 (χ (2) p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (χ (2) p = 0.00001). The A-allele of FTO was associated with a 1.99× higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.50× higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.
体重增加，当导致超重或肥胖时，是现今主要的健康问题之一。ACE、FTO、AKR1C2、TIMP4 和 MMP2 基因已在之前的体重调节研究中被涉及。本研究调查了这些五个候选基因中的多态性对 10 年内体重增加风险的贡献。从参加多塞特队列研究的参与者中选择了两组，该研究对他们进行了 10 年的随访：体重稳定组（±2kg/10 年；n=259）和体重增加组，他们的体重增加了大约 10%（>8kg/10 年；n=237）。起始 BMI 介于 20 至 35kg/m(2) 之间，基线年龄在 20 至 45 岁之间。在每个组中测量候选基因中的选定 SNP 和插入/缺失。在男性中，FTO rs9939609（χ(2) p=0.005）、ACE rs4340（χ(2) p=0.006）和 AKR1C2 rs12249281（χ(2) p=0.019）的等位基因分布在体重稳定组和体重增加组之间不同。观察到 FTO rs9939609 和 ACE rs4340 之间的相互作用。在女性中，MMP2 rs1132896 的等位基因分布在体重稳定组和体重增加组之间不同（χ(2) p=0.00001）。FTO 的 A 等位基因与男性体重增加的风险增加 1.99 倍相关（OR 1.99，p=0.020），而在女性中，MMP2 的 C 等位基因与体重增加的风险增加 2.50 倍相关（OR 2.50，p=0.001）在 10 年期间。我们发现 FTO 在男性和 MMP2 在女性中与 10 年随访期间的体重增加有关。
