Peroxisome proliferator-activated receptor γ 2 and acyl-CoA synthetase 5 polymorphisms influence diet response
Peroxisome proliferator-activated receptor γ 2 and acyl-CoA synthetase 5 polymorphisms influence diet response
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DOI：
10.1038/oby.2007.630
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发表时间：
2007-05-01
期刊：
影响因子：
6.9
通讯作者：
Tesson, Frederique
中科院分区：
文献类型：
--
作者：
Adamo, Kristi B.;Dent, Robert;Tesson, Frederique
过氧化物酶体增殖物激活受体γ (PPAR γ)及其应答基因酰基辅酶a合成酶5 （ACSL5）在脂肪酸代谢中起重要作用，可能影响热量限制后的体重减轻。因此，我们的目的是确定这些基因是否参与对饮食治疗的个体间反应。在900千卡配方饮食的前6周，从体重减轻最多的五分之一（饮食反应性，n = 74）和体重减轻最少的五分之一（饮食抵抗性，n = 67）中选择肥胖妇女进行基因型/表型比较。选择两个常见的PPAR γ单核苷酸多态性，Pro(12)Ala和C1431T，以及8个跨ACSL5基因的多态性进行单位点和单倍型关联分析。PPAR γ Pro(12)Ala单核苷酸多态性与饮食抵抗相关（比值比为3.48,95%可信区间为1.41 ~ 8.56,p = 0.03），位于ACSL5基因5′非翻译区rs2419621与饮食反应相关最强（比值比为3.45,95%可信区间为1.61 ~ 7.69,p = 0.001）。与变异rs2419621等位基因相比，野生型携带者骨骼肌ACSL5 mRNA表达量显著降低（p = 0.03）。我们的研究结果表明PPAR γ 2和ACSL5基因型与饮食反应性之间存在联系。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) and its response gene, Acyl CoA synthetase 5 (ACSL5), which has an important role in fatty acid metabolism, may affect weight loss in response to caloric restriction. Therefore, we aimed to determine whether these genes were involved in the interindividual response to dietary treatment. Genotypic/ phenotypic comparisons were made between selected obese women from the quintiles losing the most (diet responsive, n = 74) and the quintiles losing the least (diet-resistant, n = 67) weight in the first 6 weeks of a 900-kcal formula diet. Two common PPAR gamma single nucleotide polymorphisms, Pro(12)Ala and C1431T, and eight polymorphisms across the ACSL5 gene were selected for single locus and haplotypic association analyses. The PPAR gamma Pro(12)Ala single nucleotide polymorphism was associated with diet resistance (odds ratio = 3.48, 95% confidence interval = 1.41 to 8.56, p = 0.03), and the rs2419621, located in the 5' untranslated region of the ACSL5 gene, displayed the strongest association with diet response (odds ratio = 3.45, 95% confidence interval = 1.61 to 7.69, p = 0.001). Skeletal muscle ACSL5 mRNA expression was significantly lower in carriers of the wildtype compared with the variant rs2419621 allele (p = 0.03). Our results suggest a link between PPAR gamma 2 and ACSL5 genotype and diet responsiveness.