Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study

Data were collected from community-dwelling Japanese adults aged 40-84 years who participated in the Longitudinal Study of Aging biennially between 1997 and 2008. We analyzed cumulative data (5,167 samples in accumulated total) using generalized estimating equations.The MTHFR 677T allele was significantly associated with a reduced risk of hearing impairment only when the subjects were wild-type homozygotes for MTR A2756G. The per-T allele odds ratio of MTHFR for the risk of developing hearing impairment was 0.7609 (95% CI: 0.6178-0.9372) in the MTR AA genotype. In addition, a subgroup analysis demonstrated that the favorable effect of the MTHFR 677T allele on the risk of developing hearing impairment was independent of folate and homocysteine level, whereas plasma total homocysteine level was independently associated with an increased risk of developing hearing impairment. The interactive effect of gene polymorphisms associated with folate metabolism may modify the risk of developing hearing impairment after middle age. These results contribute to the elucidation of the causes of ARHI.The present study has found that the MTHFR 677T allele has a favorable effect on a risk of hearing impairment in the middle-aged and elderly population, only when the individuals were wild-type homozygotes for MTR A2756G.Presbycusis is one of the most common sensory impairments affecting the elderly and is a multifactorial process that involves a multitude of intrinsic and extrinsic factors. Recent investigations demonstrated many genetic contributions to human age-related hearing impairment (ARHI) [1-7].Folate metabolism is essential for cellular functioning because it provides one-carbon donors for the de novo synthesis of purines and pyrimidines, which are necessary for RNA and DNA synthesis, and provides methyl groups, which are necessary for the remethylation of homocysteine and for methylation reactions such as DNA methylation [8,9]. The enzyme methylenetetrahydrofolate reductase