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.
Highlights
Age-related hearing impairment (ARHI), known as presbycusis, is a multifactorial symmetric sensorineural loss that affects adults older than 50 years of age [1]
The potassium voltage-gated channel member 4 gene (KCNQ4,OMIM ID:603537) [16]; N-acetyltransferases (NAT2*6A,OMIM ID:612182) [17,18,19]; the grainyhead-like 2 gene (GRHL2,OMIM ID: 608576) [20]; the apolipoprotein E gene (APOE ε4 OMIM ID: 107741) [21]; the endothelin-1 gene (EDN1, OMIM ID: 131240) [22,23]; the uncoupling protein gene (UCP2, OMIM ID: 601693) [24] and the mitochondrial DNA 4977 common deletion [25,26] have all been reported to be correlated with ARHI
A total of 1306 male volunteers met the selection criteria: 324 subjects were assigned to the healthy control group, and 982 individuals were deemed eligible for ARHI case group in this study
Summary
Age-related hearing impairment (ARHI), known as presbycusis, is a multifactorial symmetric sensorineural loss that affects adults older than 50 years of age [1]. Association studies have attempted to identify genetic variations that occur more frequently in unrelated affected compared to unrelated, unaffected individuals [11,12]. Research done by Friedman et al [27] provided convincing evidence that variations in glutamate metabotrophic receptor 7 (GRM7, OMIM ID: 604101) was associated with ARHI in older European adults. Newman et al [29] explored the relationship of the GRM7 haplotypes and SNP genotypes with various measures of auditory perception in a EuropeanAmerican population. In another GWAS study, a Finnish Saami population was scrutinized for individuals with ARHI [28]. Similar research has not yet been reported in the Asian Han population
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