Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case–control study

Caliskan, Metin; Boyacioglu, Olcay; Coskunoglu, Aysun; Bozkurt, Gökay; Çam, Fethi Sırrı

doi:10.1007/s11033-019-04837-0

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…The CpG sites are deoxyribonucleic acid (DNA) regions in which cytosine and guanine nucleotides exist in succession, and are sites that can regulate gene expression through methylation of cytosine. In fact, a comparison of the methylation of 12 CpG sites in the BDNF and GDNF promoter regions in patients with chronic tinnitus and the control group, there was a difference in the methylation ratio of BDNF CpG6 and GDNF CpG3-5-6 between the two groups [ 94 ]. Serotonin is an important neurotransmitter that is mainly present at the nerve endings in the central and peripheral nervous systems and plays an important role in the activation of the limbic and reticular brain structures that regulate the contraction and dilatation of blood vessels.…”

Section: Biomarkers In Chronic Subjective Tinnitusmentioning

confidence: 99%

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

Kang

Kim

Park

et al. 2021

IJMS

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Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.

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Section: Biomarkers In Chronic Subjective Tinnitusmentioning

confidence: 99%

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

Kang

Kim

Park

et al. 2021

IJMS

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“…All the studies included reported no significant differences in terms of age between subgroups. Three studies excluded patients with SNHL [ 36 , 42 , 47 ], two studies reported no significant differences in audiograms between tinnitus and control subjects [ 39 , 40 ], six studies included subjects with some degree of hearing impairment, including SNHL [ 8 , 37 , 45 , 49 ], presbycusis [ 35 ], or noise-induced hearing loss [ 41 ], and the rest of them failed to report information on hearing stage [ 9 , 38 , 43 , 44 , 46 , 48 ].…”

Section: Resultsmentioning

confidence: 99%

“…These genetic studies included four genome-wide association studies (GWAS) using genotyping arrays [ 9 , 41 , 46 , 47 ], nine candidate gene studies [ 35 , 36 , 38 – 40 , 42 , 43 , 45 , 48 ], two sequencing studies using exome sequencing [ 8 ] and genome-sequencing data [ 49 ], and one mitochondrial DNA sequencing study [ 37 ]. Besides, there was a methylation study in the BDNF and GDNF genes [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…In Polish HL patients with tinnitus, m.7511 T > C was significantly more frequent than in patients without tinnitus ( p = 0.0441) No Orenay-Boyacioglu et al [ 38 ] Turkey Genotyping case–control study GDNF To investigate the role of GDNF polymorphisms in tinnitus pathophysiology n = 94; cases: 52; controls: 42 Cases: 33 M–19F; controls: 29 M–13F Cases: 43.6 ± 10.7; controls: 39.3 ± 9.8 Cases: 100%; controls: 0% N/A No association was found for rs884344 and rs3812047 and subjects with tinnitus. Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls ( p = 0.02) No Orenay-Boyacioglu et al [ 44 ] WGBS specific regions BDNF , GDNF To study the relationship between the promotor methylation of BDNF and GDNF genes and chronic tinnitus in peripheral blood samples n = 110; cases: 60; controls: 50 Cases: 39 M–21F; controls: 31 M–19F Cases: 36.5 (21–52); controls: 38.5 (23–54) Cases: 100%; controls: 0% N/A Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5–6 methylation ratios in the comparison of control group and the chronic tinnitus patients ( p = 0.002, 0.0005, 0.00003, and 0.0029, respectively) No Rottenberg et al [ 45 ] Slovenia Genotyping case–control study GABA(A ) beta-3 subunit gene To explore associations between manifestation of tinnitus, auditory evoked potentials and genetic background of gamma-aminobutyric acid type A (GABA(A) receptors) to support the disinhibited feedback hypothesis of tinnitus generation n = 131 Cohort: 61 M–71F Cohort: 52 ± 13.8 Cohort: 100% Cohort: 100% Statistically significant difference in the tinnitus s...…”

Section: Resultsmentioning

confidence: 99%

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A Systematic Review on the Genetic Contribution to Tinnitus

Perez-Carpena,

Lopez-Escamez,

Gallego-Martinez

2024

JARO

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Purpose To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus. Methods After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development. Results The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes. Conclusions The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.

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“…[ 67 ] However, the relationship between BDNF expression and the severity of tinnitus is still controversial. Some studies found that the BDNF concentration in the tinnitus group was higher than that in the normal control group,[ 64 ] but others have found otherwise. [ 56 ] Some studies have found that the BDNF levels were not related to the severity of tinnitus,[ 50 ] whereas some others have shown that BDNF concentration in the mild tinnitus group was higher than that in the severe tinnitus and the normal control groups.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Studies in Tinnitus-Related Gene Research

Zhong

Zeng

et al. 2021

Noise and Health

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Objective: Summarize and analyze the current research results of tinnitus-related genes, explore the potential links between the results of each study, and provide reference for subsequent studies. Methods: Collect and sort out the research literature related to tinnitus genes included in PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform before December 31, 2019. Then the relevant contents of the literature were sorted out and summarized. Results: Fifty-one articles were finally selected for analysis: 31 articles (60.8%) were classified as researches on animal models of tinnitus, and 20 (39.2%) as researches on tinnitus patients. Existing studies have shown that genes related to oxidative stress, inflammatory response, nerve excitation/inhibition, and nerve growth are differentially expressed in tinnitus patients or animal models, and have presented the potential links between genes or proteins in the occurrence and development of tinnitus. Conclusion: The research on tinnitus-related genes is still in the exploratory stage, and further high-quality research evidence is needed.

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Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case–control study

Cited by 11 publications

References 22 publications

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

A Systematic Review on the Genetic Contribution to Tinnitus

Analysis of Studies in Tinnitus-Related Gene Research

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