Corella Dolores, Qi Lu, Sorlí José V, Godoy Diego, Portolés Olga, Coltell Oscar, Greenberg Andrew S, Ordovas José M
Nutrition and Genomics Laboratory, Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, Massachusetts 02111, USA.
J Clin Endocrinol Metab. 2005 Sep;90(9):5121-6. doi: 10.1210/jc.2005-0576. Epub 2005 Jun 28.
Dietary treatment of obesity could be improved if predictive information about the individual's genetic response to diet was available. Adipose tissue has been the focus of efforts to identify candidate genes. Perilipin is a major protein found in adipocytes, and perilipin knockout mice are lean and resistant to diet-induced obesity.
The objective of the study was to examine the association of several polymorphisms at the perilipin (PLIN) locus with obesity and weight reduction in response to a low-energy diet in obese patients.
This study was a 1-yr randomized (depending on the PLIN genotype) trial with three follow-up evaluations.
The study was conducted at a university research center.
One hundred fifty obese patients (body mass index, 42 +/- 8 kg/m2) at baseline and 48 patients who completed the dietary follow-up treatment for weight loss participated in the study.
Subjects completed a 1-yr low-energy diet.
Body weight (BW) at baseline and 3, 6, and 12 months was measured.
The minor A-allele at the PLIN 11482G>A polymorphism was associated with lower baseline BW. Moreover, we found a gene-diet interaction (P = 0.015) between this polymorphism and weight loss in patients that completed the 1-yr dietary treatment. Diet resulted in significant decreases in BW (from 114.3 +/- 3.9 kg at baseline to 105.5 +/- 3.5 kg at 1 yr; P lineal trend, 0.020) in GG patients (n = 33). Conversely, carriers of the minor A allele (n = 15) did not show significant changes in BW (from 105.0 +/- 4.6 kg at baseline to 104.3 +/- 4.4 kg at 1 yr; P lineal trend, 0.985). This gene-diet interaction remained statistically significant, even after adjustment for differences in BW at baseline and for other potential confounders.
PLIN11482A carriers were resistant to weight loss, suggesting that this polymorphism may predict outcome of BW reduction strategies based on low-energy diets.
如果能够获得个体对饮食的基因反应的预测信息，肥胖的饮食治疗可能会得到改善。脂肪组织一直是寻找候选基因的重点。围脂滴蛋白是脂肪细胞中发现的一种主要蛋白质，围脂滴蛋白基因敲除小鼠体型瘦且对饮食诱导的肥胖具有抗性。
本研究的目的是检测肥胖患者中围脂滴蛋白（PLIN）基因座的几种多态性与肥胖及低能量饮食减重反应之间的关联。
本研究是一项为期1年的随机（取决于PLIN基因型）试验，进行了三次随访评估。
该研究在一所大学研究中心进行。
150名肥胖患者（基线时体重指数为42±8kg/m²）以及48名完成减重饮食随访治疗的患者参与了本研究。
受试者完成了为期1年的低能量饮食。
测量基线时、3个月、6个月和l2个月时的体重（BW）。
PLIN 11482G>A多态性的次要A等位基因与较低的基线体重相关。此外，我们发现该多态性与完成1年饮食治疗的患者体重减轻之间存在基因-饮食相互作用（P=0.015）。饮食导致GG患者（n=33）体重显著下降（从基线时的114.3±3.9kg降至1年时的105.5±3.5kg；线性趋势P=0.020）。相反，次要A等位基因携带者（n=15）的体重没有显著变化（从基线时的105.0±4.6kg降至1年时的104.3±4.4kg；线性趋势P=0.985）。即使在对基线体重差异和其他潜在混杂因素进行校正后，这种基因-饮食相互作用仍具有统计学意义。
PLIN11482A携带者对体重减轻具有抗性，提示该多态性可能预测基于低能量饮食的体重减轻策略的效果。
