Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu City, Aichi Prefecture 474-8511, Japan.
BMC Med Genet. 2011 Mar 7;12:35. doi: 10.1186/1471-2350-12-35.
Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI), however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular functioning. Despite the extensive investigations regarding the roles of folate metabolism related gene polymorphisms in the pathophysiology of complex diseases, such as cancer, cardio-cerebrovascular disease, and atherosclerosis, little is known about the association with ARHI. The aim of this study is to investigate the effects of the methionine synthase (MTR) A2756G and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms on the risk of hearing impairment in middle-aged and elderly Japanese.
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.
最近的研究表明，许多遗传因素都与人类年龄相关性听力损失（ARHI）的发展有关，但是，有关降低 ARHI 风险的因素的报告却很少。叶酸代谢对于细胞功能至关重要。尽管广泛研究了叶酸代谢相关基因多态性在癌症、心脑血管疾病和动脉粥样硬化等复杂疾病的病理生理学中的作用，但对于其与 ARHI 的关联知之甚少。本研究旨在探讨蛋氨酸合成酶（MTR）A2756G 和亚甲基四氢叶酸还原酶（MTHFR）C677T 基因多态性对日本中老年人听力损失风险的影响。
本研究的数据来自于 1997 年至 2008 年间参加了纵向老龄化研究的社区居住的日本成年人，这些成年人年龄在 40-84 岁之间，每两年参加一次研究。我们使用广义估计方程分析了累积数据（共 5167 个样本）。
仅当研究对象为 MTR A2756G 野生型纯合子时，MTHFR 677T 等位基因才与听力损失风险降低显著相关。在 MTR AA 基因型中，MTHFR 677T 等位基因对听力损失风险的每一个 T 等位基因比值比为 0.7609（95%CI：0.6178-0.9372）。此外，亚组分析表明，MTHFR 677T 等位基因对听力损失风险的有利影响独立于叶酸和同型半胱氨酸水平，而血浆总同型半胱氨酸水平与听力损失风险增加独立相关。与叶酸代谢相关的基因多态性的相互作用可能会改变中年后听力损失的风险。这些结果有助于阐明 ARHI 的病因。
本研究发现，只有当个体为 MTR A2756G 野生型纯合子时，MTHFR 677T 等位基因对中老年人的听力损失风险有有利影响。
