Genetic polymorphisms of the enzymes involved in DNA methylation ans synthesis in elite atletes

Physical exercise induces adaptive changes leading to a muscle phenotype with an enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT) and 68-bp ins of cystathionine β-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG) and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared to the control group (p=0.0001; p=0.018 and p=0.0001) suggesting a reduced DNA methylating capacity. We then therefore assessed whether assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6) and late phase (MHC) of myogenesis, in a cellular model of hypomethylated or un-hypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells (F.C.=Myf-5:1.21, 1.35; MyoD:0.9, 1.47; Myf-6:1.39, 1.66; MHC:1.35, 3.10 in GMA, DMA respectively) compared with the control groups (F.C.=Myf-5:1.0, 1.38; MyoD:1.0, 1.14; Myf-6:1.0, 1.44; MHC:1.0, 2.20 in GM, DM respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS and MSR enzymes, induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass.