Angiotensin-Converting Enzyme (ACE) I/D and Alpha-Adducin (ADD1) G460W Gene Polymorphisms in Turkish Patients with Severe Chronic Tinnitus

Abstract

OBJECTIVE:Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. MATERIALS and METHODS:The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. RESULTS:With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (p<0.01) and allele frequencies (p=0.021) of the ADD1 G460W gene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (p<0.01). CONCLUSION:Our results demonstrate an association between ADD1 G460W gene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.

Genetics of Tinnitus: Still in its Infancy

“…Tinnitus candidate gene selection has included genes enriched in cardiovascular function ( ACE, ADD1 ), neurotrophic factors ( BDNF, GDNF ), ion recycling pathways ( KCNE1, KCNE3, SLC12A2 ), GABA B receptor subunit ( KCTD12 ), and serotonin receptor/transporter ( HTR1A, SLC6A4 ) function. Presently, nine case-control studies have examined a combined total of 18 genes that are summarized in Table 2 (Kleinjung et al, 2006; Deniz et al, 2010; Sand et al, 2010, 2011, 2012a,b; Pawełczyk et al, 2012; Orenay-Boyacioglu et al, 2016; Yüce et al, 2016). For brevity, we describe selected case-control association studies with potentially significant results.…”

“…Hypertension-associated auditory primary lesion sites are the organ of Corti and stria vascularis (Gates et al, 1993). An association study investigated the relationship between severe chronic tinnitus and the p.G460W polymorphism in 89 patients with severe chronic tinnitus and 104 age-matched Turkish-Caucasian controls (Yüce et al, 2016). Clinical tinnitus evaluation and severity assessment were performed by the Structured Tinnitus Interview and the Tinnitus Handicap Inventory, respectively.…”

“…Clinical tinnitus evaluation and severity assessment were performed by the Structured Tinnitus Interview and the Tinnitus Handicap Inventory, respectively. PCR-based restriction fragment length polymorphism (RFLP) analysis of the ADD1 GW genotype ( p = 0.009, χ 2 = 9.4) and the W allele ( p = 0.021, χ 2 = 5.3) revealed significantly increased allele frequencies in the patient group (Yüce et al, 2016). This study asserted the potential involvement of the p.G460W genotype and W allele in ADD1 in tinnitus pathophysiology.…”

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

“…Este tipo de estudio sólo permite identificar variantes ligadas a un gen concreto y requieren estudios a escala genómica previa para proponer genes candidatos. Por otra parte, la selección de variantes puede presentar un sesgo de selección, por la asociación entre el marcador genético en estudio y la variante genética de riesgo verdadera (desequilibrio de ligamiento), resultando difícil determinar cuál es la variante que confiere el riesgo para la fenotipo (21) Hasta ahora se han realizado 9 estudios de casos-control con 18 genes candidatos (10)(11)(12)(13)(22)(23)(24)(25)(26). (Tabla 1).…”

Genetic variation in RCOR1 is associated with tinnitus in UK Biobank

“…Identification of the genetic variants involved in tinnitus would help reveal the nature of the mechanisms involved in generating tinnitus after hearing loss, a pre-requisite for development of treatments. Previous pilot genome-wide association studies and candidate gene studies for tinnitus 10; 13-18 have lacked sufficient power to establish specific genetic risk factors but the relatively high heritability demonstrates there is potential to use such approaches to reveal the underlying mechanisms 9; 10 . On this basis we performed a genome-wide association study using self-reported tinnitus available from 172,608 UK Biobank (UKBB) 19 volunteers.…”