Association of GRM7 Variants with Different Phenotype Patterns of Age-Related Hearing Impairment in an Elderly Male Han Chinese Population

Several single nucleotide polymorphisms (SNPs) of the Glutamate metabotrophic receptor 7 gene (GRM7) have recently been identified by the genome-wide association study (GWAS) as potentially playing a role in susceptibility to age-related hearing impairment (ARHI), however this has not been validated in the Han Chinese population. The aim of this study was to determine if these SNPs are also associated with ARHI in an elderly male Han Chinese population. In this case-control candidate genes association study, a total of 982 men with ARHI and 324 normal-hearing controls subjects were studied. Using K-means cluster analysis, four audiogram shape subtypes of ARHI were identified in the case group: ‘‘flat shape (FL)’’, ‘‘sloping shape (SL)’’, ‘‘2-4 kHz abrupt loss (AL) shape’’ and ‘‘8 kHz dip (8D) shape’’. Results suggested that the SNP rs11928865 (A>T) of GRM7 was significantly associated with ARHI after adjusting for non-genetic factors (p= 0.000472, OR= 1.599, 95%CI= 1.229~2.081). Furthermore, frequency of TT genotype (rs11928865) were significant higher in the SL subgroup and AL subgroup with compared to controls group (p= 9.41E-05, OR= 1.945, 95%CI= 1.393~2.715; p= 0.000109, OR= 1.915, 95%CI= 1.378~2.661 adjusted, respectively) after Bonferroni correction. However, there wasn’t significant difference in the frequency of the TT genotype between cases in the FL subgroup or the 8D subgroup with when compared with controls. Results of the current study suggest that, in an elderly male Han Chinese population, GRM7 SNP rs11928865 (TT) occurs more frequently in ARHI patients with SL and AL phenotype patterns.

近期，全基因组关联研究（genome-wide association study, GWAS）已在代谢型谷氨酸受体7基因（glutamate metabotrophic receptor 7 gene, GRM7）中鉴定出若干单核苷酸多态性（single nucleotide polymorphisms, SNPs），上述位点或与年龄相关性听力损失（age-related hearing impairment, ARHI）的易感性相关，但该结论尚未在汉族人群中得到验证。本研究旨在探讨上述SNPs在老年男性汉族人群中是否与ARHI存在关联。本项病例对照候选基因关联研究共纳入982名ARHI患者与324名听力正常的对照受试者。通过K均值聚类分析，病例组中共识别出4种ARHI听力图形态亚型：平坦型（FL）、斜坡型（SL）、2-4kHz骤降型（AL）以及8kHz谷值型（8D）。分析结果显示，在校正非遗传因素后，GRM7基因的rs11928865（A>T）位点与ARHI存在显著关联（p=0.000472，比值比（odds ratio, OR）=1.599，95%置信区间（confidence interval, CI）=1.229~2.081）。进一步分析表明，经邦费罗尼校正后，SL亚型与AL亚型病例组中rs11928865的TT基因型频率均显著高于对照组（分别为p=9.41×10⁻⁵，OR=1.945，95%CI=1.393~2.715；p=0.000109，OR=1.915，95%CI=1.378~2.661，均已完成校正）。而FL亚型与8D亚型病例组的TT基因型频率与对照组相比无显著差异。本研究结果提示，在老年男性汉族人群中，GRM7基因rs11928865位点的TT基因型在表现为SL和AL表型的ARHI患者中分布频率更高。