Biomarkers of Presbycusis and Tinnitus in a Portuguese Older Population

Abstract

Introduction: Presbycusis or age-related hearing loss (ARHL) is a ubiquitous health problem. It is estimated that it will affect up to 1.5 billion people by 2025. In addition, tinnitus occurs in a large majority of cases with presbycusis. Glutamate metabotropic receptor 7 (GRM7) and N-acetyltransferase 2 (NAT2) are some of the genetic markers for presbycusis.Objectives: To explore patterns of hearing loss and the role of GRM7 and NAT2 as possible markers of presbycusis and tinnitus in a Portuguese population sample.Materials and Methods: Tonal and speech audiometry, tinnitus assessment, clinical interview, and DNA samples were obtained from patients aged from 55 to 75 with or without tinnitus. GRM7 analysis was performed by qPCR. Genotyping of single nucleotide polymorphisms (SNPs) in NAT2 was performed by PCR amplification followed by Sanger sequencing or by qPCR.Results: We screened samples from 78 individuals (33 men and 45 women). T allele at GRM7 gene was the most observed (60.3% T/T and 33.3% A/T). Individuals with a T/T genotype have a higher risk for ARHL and 33% lower risk for tinnitus, compared to individuals with A/A and A/T genotype, respectively. Being a slow acetylator (53%) was the most common NAT2 phenotype, more common in men (55.8%). Intermediate acetylator was the second most common phenotype (35.9%) also more frequent in men (82.6%). Noise exposed individuals and individuals with ‘high frequency’ hearing loss seem to have a higher risk for tinnitus. Our data suggests that allele AT of GRM7 can have a statistically significant influence toward the severity of tinnitus.Conclusion: For each increasing year of age the chance of HL increases by 9%. The risk for ARHL was not significantly associated with GRM7 neither NAT2. However, we cannot conclude from our data whether the presence of T allele at GRM7 increases the odds for ARHL or whether the A allele has a protective effect. Genotype A/T at GRM7 could potentially be considered a biomarker of tinnitus severity. This is the first study evaluating the effect of GRM7 and NAT2 gene in tinnitus.

Genetics of age‐related hearing loss

“…The latest study to assess GRM7 risk variants in an ARHL population sample tested four SNPs in elderly Taiwanese and found one associated in a dominant pattern (Chang et al, 2018). Two studies have analyzed GRM7 risk variants in relation to traits linked to ARHL; noise-induced HL in a Han Chinese sample (Yu et al, 2018) and tinnitus and ARHL in a Portuguese sample (Haider et al, 2017).…”

Presbycusis-Related Tinnitus and Cognitive Impairment: Gender Differences and Common Mechanisms

“…Several researches suggest that hearing loss contributes to the higher prevalence of tinnitus [33]. At present, the following two reasons are mostly considered.…”

“…Clinically, patients with presbycusis usually perform worse than others in function of speech and communication, resulting in negative psychosocial endings such as social isolation and social frailty [40]; depression, poor cognitive performance and even induce cognitive decline [33,41]; and low physical performance and physical frailty [42,43]. A meta-analysis of 36 epidemiological studies and 20,264 participants showed that the decline of cognitive domains are significantly associated with ARHL [44].…”

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

“…Individual differences in the presentation, duration and frequency of these phantom sounds suggests that tinnitus is likely to be a heterogeneous condition representing a range of pathologies. It often manifests as secondary to hearing loss in both permanent hearing loss or temporary loss secondary to recreational or occupational noise exposure 1 – 7 . Although most individuals with tinnitus also have a hearing loss, tinnitus can occur in isolation 2 , 3 The relative contributions of the central and peripheral auditory system to tinnitus remain uncertain but evidence suggests that acute temporary tinnitus after noise exposure is likely to reflect cochlear damage while long term chronic tinnitus has been shown to involve re-organisation or disturbance of neurons in the primary auditory cortex owing to a lack of signal from the cochlea 1 , 8 .…”