Table 2.
Genes screened in tinnitus candidate gene studies.
| Gene | MIM | Gene function | Number of subjects | Phenotype | Method | Outcome | Stastical power | Multiple testing correction | References |
|---|---|---|---|---|---|---|---|---|---|
| CARDIOVASCULAR ASSOCIATED GENES | |||||||||
| ACE | 106180 | Angiotensin I converting enzyme | 89 | Severe chronic tinnitus | PCR-RFLP genotyping | -No significance | Not described | Not described | Yüce et al., 2016 |
| ADD1 | 102680 | Adducin 1 | 89 | Severe chronic tinnitus | PCR-RFLP genotyping | -The p.G460W heterozygous genotype (p = 0.009) and W allele (p = 0.021) are statistically significantly higher in patients than controls | Not described | Not described | Yüce et al., 2016 |
| NEUROTROPHIC FACTORS | |||||||||
| BDNF | 113505 | Brain derived neurotrophic factor | 240 | Chronic tinnitus | PCR-RFLP genotyping | -No correlation between tinnitus and rs2049046 and rs6265 polymorphisms | Underpowered, nearly 15,000 patients and >680,000 controls required for exclusion of a modifying risk from rs6265 | Yes | Sand et al., 2012b |
| GDNF | 600837 | Glial cell derived neurotrophic factor | 52 | Chronic tinnitus | PCR-RFLP genotyping | -No correlation between tinnitus and rs884344, rs3812047 and rs1110149 polymorphisms -Heterozygosity was significantly lower (p = 0.02) for rs1110149 between patients and controls | Not described | Not described | Orenay-Boyacioglu et al., 2016 |
| 240 | Chronic tinnitus | PCR-RFLP genotyping | -No correlation between tinnitus and rs1110149, rs884344 and rs3812047 polymorphisms | Underpowered | Yes | Sand et al., 2012b | |||
| POTASSIUM RECYCLING PATHWAY GENES | |||||||||
| KCNE1 | 176261 | Potassium voltage-gated channel subfamily E regulatory subunit 1 | 201 | Chronic tinnitus | Sanger sequencing | -No correlation between tinnitus severity and 46 polymorphic variants -V47I novel variant detected | Underpowered, >12,500 patients required to exclude a modifying allele risk | No | Sand et al., 2010 |
| 128 | Noise exposed males with tinnitus | SNP genotyping | -Significance was detected in rs915539 (p = 0.005) in noise-resistant subjects and when comparing tinnitus patients vs. controls in noise-resistant and susceptible groups (p = 0.018) | Not described | No | Pawełczyk et al., 2012 | |||
| KCNE3 | 604433 | Potassium voltage-gated channel subfamily E regulatory subunit 3 | 288 | Chronic tinnitus | Sanger sequencing | -No association between tinnitus and 11 polymorphic variants | Underpowered, 2,707 patients and 65,083 controls required | No | Sand et al., 2011 |
| SLC12A2 | 600840 | Solute carrier family 12 member 2 | 128 | Noise exposed males with tinnitus | SNP genotyping | -Significance was detected in rs10089 (p = 0.016) in noise susceptible subjects and when comparing tinnitus patients vs. controls in noise-resistant and susceptible groups (p = 0.026) | Not described | No | Pawełczyk et al., 2012 |
| GABAB RECEPTOR SUBUNIT | |||||||||
| KCTD12 | 610521 | Potassium channel tetramerization domain containing 12 | 95 | Chronic tinnitus | Sanger sequencing | -rs34544607 was associated with tinnitus (p = 0.04) but weakened after screening 50 additional cases (p = 0.07) | Underpowered, 363 tinnitus cases required | No | Sand et al., 2012a |
| -Gene did not predict tinnitus severity | |||||||||
| SEROTONIN RECEPTOR/TRANSPORTER | |||||||||
| HTR1A | 109760 | 5-hydroxytrypthamine receptor 1A | 88 | Chronic tinnitus | Sanger sequencing | -No correlation between tinnitus and rs1800043 polymorphism | Not described | Not described | Kleinjung et al., 2006 |
| SLC6A4 | 182138 | Solute carrier family 6 member 4 | 54 | Chronic tinnitus | PCR and VNTR analysis | -Association between quality of life scores (severity, p = 0.004; tinnitus discomfort level, p = 0.002; attention deficit, p = 0.04; sleep disorder, p = 0.04) and patients with the 5-HTTLPR polymorphism | Not described | Not described | Deniz et al., 2010 |
PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism; VNTR: variable number tandem repeat
The study from Pawełczyk et al. also included the analysis of eight further genes involved in the potassium recycling pathway (GJB1, GJB2, GJB3, GJB4, GJB6, KCNJ10, KCNQ1, KCNQ4) but results were not significant (Pawełczyk et al., 2012).