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Exercise training, genetics and type 2 diabetes‐related phenotypes
Author(s) -
Hagberg J. M.,
Jenkins N. T.,
Spangenburg E.
Publication year - 2012
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2012.02455.x
Subject(s) - type 2 diabetes , phenotype , genome wide association study , biology , genetics , type 2 diabetes mellitus , candidate gene , genetic association , locus (genetics) , bioinformatics , genotype , medicine , diabetes mellitus , gene , single nucleotide polymorphism , endocrinology
Type 2 diabetes mellitus (T2 DM ) 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 T2 DM 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 T2 DM ‐related phenotypes, there is substantial interindividual variation in these responses. There is some evidence that T2 DM ‐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 T2 DM ‐related phenotype responses to exercise training. From candidate gene studies, there are relatively strong and replicated data supporting a role for the PPAR γ Pro12Ala variant in the interindividual differences in T2 DM ‐related phenotype responses to training. This is a potentially important candidate locus because it affects T2 DM susceptibility, has high biological plausibility and is the target for the primary pharmaceutical method for treating T2 DM . Is it time to conduct a hypothesis‐driven large‐scale exercise training intervention trial based on PPAR γ Pro12Ala genotype with T2 DM ‐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 PPAR γ Pro12Ala genotype and exercise training?