Association of GRM7 variants with different phenotype patterns of age-related hearing impairment in an elderly male Han Chinese population

PLoS One. 2013 Oct 11;8(10):e77153. doi: 10.1371/journal.pone.0077153. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • Audiometry
  • Case-Control Studies
  • China
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Variation*
  • Genotype
  • Hearing Loss / diagnosis*
  • Hearing Loss / genetics*
  • Humans
  • Male
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Receptors, Metabotropic Glutamate / genetics*

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 7

Grants and funding

This research was supported by a grant from National Basic Research Program of China 2011CB504501 (HW); grant from the Research Special Fund for Public Welfare Industry of Health, Ministry of Health of China No. 201202005 (HW); grant from the 12th Five-Year National Key Technologies Research & Development program No. 2012BAI12B01 (ZH); grants from National Science Foundation of China 81222010 (TY) and grants from Shanghai Municipal Science and Technology Commission 11PJ1407000 (TY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.