Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes.
Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes.
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作者：
Haupt A;Thamer C;Heni M;Ketterer C;Machann J;Schick F;Machicao F;Stefan N;Claussen CD;Häring HU;Fritsche A;Staiger H
糖尿病风险基因转录因子7样2（TCF 7 L2）对体重的影响尚不清楚。由于TCF 7 L2在脂肪组织中表达，并参与Wnt依赖的脂肪形成调节，我们研究了TCF 7 L2变体对生活方式干预期间身体组成和体重减轻的影响。我们对309名2型糖尿病风险增加的德国受试者进行了TCF 7 L2单核苷酸多态性（SNP）rs7903146、rs 12255372、rs 11196205和rs7895340基因分型，并在9个月的生活方式干预前后进行了口服葡萄糖耐量试验。使用全身磁共振成像/光谱法对210例受试者的脂肪分布进行定量。调整混杂变量后，我们观察到2型糖尿病SNP rs7903146等位基因对生活方式干预期间BMI（P = 0.0034）和非内脏脂肪（P = 0.0032）和内脏脂肪（P = 0.0165）变化的负面影响。未检测到rs7903146与生活方式干预诱导的胰岛素分泌、葡萄糖浓度、肝脏脂肪或胰岛素敏感性变化的相关性（均P > 0.2）。用SNP rs 1255372获得了基本相同的结果。相比之下，我们没有发现SNPs rs 11196205和rs7895340对BMI变化的影响（所有P ≥ 0.5）。我们的数据显示，糖尿病相关的TCF 7 L2等位基因与生活方式干预引起的体重减轻较少相关。因此，糖尿病相关的TCF 7 L2基因变异预测了生活方式干预在减肥方面的成功，并决定了个体对环境因素的易感性。
The impact of the diabetes risk gene transcription factor 7-like 2 (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and involved in Wnt-dependent regulation of adipogenesis, we studied the impact of TCF7L2 variants on body composition and weight loss during lifestyle intervention. We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention. Fat distribution was quantified using whole-body magnetic resonance imaging/spectroscopy in a subgroup of 210 subjects. After adjustment for confounding variables, we observed a negative impact of the type 2 diabetes allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle intervention. An association of rs7903146 with lifestyle intervention-induced changes in insulin secretion, glucose concentrations, liver fat, or insulin sensitivity were not detected (all P > 0.2). Essentially the same results were obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205 and rs7895340 on change in BMI (all P ≥ 0.5). Our data reveal that diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene variation predicts the success of lifestyle intervention in terms of weight loss and determines individual susceptibility toward environmental factors.
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