Reinehr T, Friedel S, Mueller T D, Toschke A M, Hebebrand J, Hinney A
Department of Pediatric Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Witten, Germany.
Int J Obes (Lond). 2008 Oct;32(10):1521-4. doi: 10.1038/ijo.2008.146. Epub 2008 Sep 2.
The T allele of the single-nucleotide polymorphism rs7903146 in TCF7L2 (transcription factor 7 like 2 gene) is associated with type 2 diabetes mellitus. The aim of this study was to analyze whether there is an allele-dosage effect on changes of insulin resistance and sensitivity indices in overweight children participating in a lifestyle intervention.
We genotyped rs7903146 in 236 overweight children (mean age 10.7 years, mean body mass index (BMI) 28.1 kg/m2) completing a 1-year lifestyle intervention. Degree of overweight as BMI-SDS, homeostasis model assessment for insulin resistance (HOMA-IR) and the insulin sensitivity index QUICKI were measured before and after intervention.
Lifestyle intervention resulted in an overweight reduction of -0.29+/-0.02 BMI-SDS. HOMA-IR (-0.63+/-0.22) and QUICKI (+0.008+/-0.003) indices improved significantly (P<0.05) in the course of the intervention in the 155 children with a decrease of BMI-SDS. There was an additive negative effect of T allele on changes of HOMA-IR (P=0.041) and QUICKI (P=0.001) in linear regression analyses adjusted to changes of weight status, age, gender and pubertal stage.
Overweight children showed a negative dosage-allele effect per T allele at single-nucleotide polymorphism rs7903146 in TCF7L2 concerning an improvement of insulin resistance and sensitivity after overweight reduction in a lifestyle intervention. This finding further suggests that this polymorphism might be involved in glucose metabolism.
转录因子7样2基因（TCF7L2）单核苷酸多态性rs7903146的T等位基因与2型糖尿病相关。本研究旨在分析参与生活方式干预的超重儿童中，该等位基因剂量对胰岛素抵抗和敏感性指标变化是否存在影响。
我们对236名完成1年生活方式干预的超重儿童（平均年龄10.7岁，平均体重指数（BMI）28.1kg/m²）的rs7903146进行基因分型。在干预前后测量超重程度（以BMI标准差评分表示，即BMI-SDS）、胰岛素抵抗稳态模型评估（HOMA-IR）和胰岛素敏感性指数QUICKI。
生活方式干预使BMI-SDS降低了-0.29±0.02。在BMI-SDS降低的155名儿童中，干预过程中HOMA-IR（-0.63±0.22）和QUICKI（+0.008±0.003）指标显著改善（P<0.05）。在根据体重状况、年龄、性别和青春期阶段变化进行调整的线性回归分析中，T等位基因对HOMA-IR（P=0.041）和QUICKI（P=0.001）的变化存在累加负效应。
在生活方式干预减轻超重后，超重儿童中TCF7L2基因单核苷酸多态性rs7903146的每个T等位基因在改善胰岛素抵抗和敏感性方面呈现负剂量-等位基因效应。这一发现进一步表明该多态性可能参与葡萄糖代谢。
