Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD 20742, USA.
Acta Physiol (Oxf). 2012 Aug;205(4):456-71. doi: 10.1111/j.1748-1716.2012.02455.x.
Type 2 diabetes mellitus (T2DM) is at virtually pandemic levels world-wide. Diabetes has been referred to as 'a geneticist's nightmare'. However, dramatic advances in our understanding of the genetics of T2DM have occurred in the past 5 years. While endurance exercise training and increased habitual physical activity levels have consistently been shown to improve or be associated with improved T2DM-related phenotypes, there is substantial interindividual variation in these responses. There is some evidence that T2DM-related phenotype responses to exercise training are heritable, indicating that they might have a genetic basis. Genome-wide linkage studies have not identified specific chromosomal loci that could account for these differences, and no genome-wide association studies have been performed relative to T2DM-related phenotype responses to exercise training. From candidate gene studies, there are relatively strong and replicated data supporting a role for the PPARγ Pro12Ala variant in the interindividual differences in T2DM-related phenotype responses to training. This is a potentially important candidate locus because it affects T2DM susceptibility, has high biological plausibility and is the target for the primary pharmaceutical method for treating T2DM. Is it time to conduct a hypothesis-driven large-scale exercise training intervention trial based on PPARγ Pro12Ala genotype with T2DM-related phenotypes as the primary outcome measures, while also assessing potential mechanistic changes in skeletal muscle and adipose tissue? Or would it be more appropriate to propose a smaller trial to address the specific skeletal muscle and adipose tissue mechanisms affected by the interaction between the PPARγ Pro12Ala genotype and exercise training?
2 型糖尿病（T2DM）在全球范围内几乎呈流行趋势。糖尿病被称为“遗传学家的噩梦”。然而，在过去的 5 年中，我们对 T2DM 遗传学的理解取得了巨大进展。虽然耐力运动训练和习惯性体力活动水平的增加一直被证明可以改善或与改善 T2DM 相关表型相关，但这些反应在个体之间存在很大差异。有一些证据表明，T2DM 相关表型对运动训练的反应是可遗传的，这表明它们可能有遗传基础。全基因组连锁研究尚未确定可以解释这些差异的特定染色体位置，也没有针对与运动训练相关的 T2DM 相关表型反应的全基因组关联研究。从候选基因研究来看，有相对较强且可重复的数据支持 PPARγ Pro12Ala 变体在 T2DM 相关表型对训练的个体差异中的作用。这是一个潜在的重要候选基因座，因为它影响 T2DM 的易感性，具有较高的生物学合理性，并且是治疗 T2DM 的主要药物方法的靶点。是否应该基于 PPARγ Pro12Ala 基因型和 T2DM 相关表型作为主要结果测量指标，针对 T2DM 相关表型对训练的个体差异进行假设驱动的大型运动训练干预试验，同时评估骨骼肌和脂肪组织中潜在的机制变化？或者，提出一个较小的试验来解决 PPARγ Pro12Ala 基因型与运动训练相互作用影响的特定骨骼肌和脂肪组织机制是否更合适？
