Genetics of Tinnitus: Still in its Infancy

Abstract

Tinnitus is the perception of a phantom sound that affects between 10 and 15% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade. Nine studies have examined genes in a case-control association approach. Recently, a genome-wide association study has highlighted several potentially significant pathways that are implicated in tinnitus. Two twin studies have calculated a moderate heritability for tinnitus and disclosed a greater concordance rate in monozygotic twins compared to dizygotic twins. Despite the more recent data alluding to genetic factors in tinnitus, a strong association with any specific genetic locus is lacking and a genetic study with sufficient statistical power has yet to be designed. Future research endeavors must overcome the many inherent limitations in previous study designs. This review summarizes the previously embarked upon tinnitus genetic investigations and summarizes the hurdles that have been encountered. The identification of candidate genes responsible for tinnitus may afford gene based diagnostic approaches, effective therapy development, and personalized therapeutic intervention.

Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms

“…While single-variant analysis did not identify significant genetic signals, we found that cumulatively, additive SNP effects explain a large portion of variance in CisIT, further supporting the hypothesis that CisIT is a polygenic trait with complex genetic underpinnings (4). Several mechanisms of tinnitus have been proposed, but no consensus on its etiology has been reached.…”

“…2,3). Nevertheless, the pathogenic mechanisms of this disorder remain poorly understood (4), and no pharmacologic agents are approved to treat tinnitus (5); treatment is typically limited to cognitive behavioral therapy and management of associated anxiety (5,6). Despite its etiologic ambiguity, several risk factors have been shown to contribute to the development of tinnitus, including age, hearing loss, and the administration of ototoxic drugs (7,8).…”

Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities

“…In addition, approximately 40% of cisplatin-treated patients (23) experience some degree of tinnitus, which occurs at a significantly higher rate than either the general population (15%; ref. 24), or in comparable cancer patients not given cisplatin-based chemotherapy (12%; ref. 25).…”

“…23,25) with one study noting that 42% of patients report tinnitus as a major symptom after dose-intensive cisplatin chemotherapy (25). In contrast, severe tinnitus occurs in only 1%-2% of the general population (24). Furthermore, cancer survivors with hearing loss, tinnitus, and neuropathy are more likely to report poorer quality of life than those with neuropathy only (26).…”

Role of inheritance in tinnitus: it is time to search the genome

“…Así, existen múltiples factores que se asocian a la aparición de acúfenos, tales como la exposición al ruido, la hipoacusia neurosensorial de alta frecuencia, el estrés, los factores de riesgo vascular (hipertensión, diabetes, dislipemia), fármacos ototóxicos o alteraciones de la articulación temporo-mandibular, entre otros. Sin embargo, recientemente se ha empezado a revisar la contribución de los factores genéticos en la aparición de los acúfenos (8). Los escasos trabajos publicados apuntan hacia una probable herencia compleja, poligénica, con penetrancia incompleta, que determinaría una susceptibilidad o predisposición genética que interactuaría con factores ambientales muy diversos como los antes señalados.…”