Impact of Methionine Synthase Gene and Methylenetetrahydrofolate Reductase Gene Polymorphisms on the Risk of Sudden Sensorineural Hearing Loss

Abstract

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG – 7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG – 3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL.

Role of Genetic and Acquired Prothrombotic Risk Factors in Genesis of Sudden Sensorineural Hearing Loss

“…Yildiz et al [2008] found a significantly higher frequency of heterozygosity for the MTHFR C677T mutation in patients with SSHL compared to controls (50.9 vs. 25%, p = 0.03). On the other hand, Gross et al [2006] and Rudack et al [2004] did not obtain significant results when studying the C677T mutation in patients with SSHL (p = 0.17 and 0.34).…”

Association of the C677T polymorphism in the methylenetetrahydrofolate reductase gene with sudden sensorineural hearing loss

“…Hyperhomocysteinemia is believed to promote atherosclerosis and atherothrombosis as risk factors for macroangiopathies such as cerebrovascular disease and coronary disease,5, 6 and for microvessel diseases such as diabetic nephropathy and retinopathy in diabetic patients 7. Although an association between SSNHL and the MTHFR C677T polymorphism in combination with some other genetic alterations has been reported,8–10 conflicting results have been presented,11 and it remains unknown whether the MTHFR C677T polymorphism is associated with SSNHL in isolation.…”

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part I.

“…Together with the increased risk for hyperhomocysteinemia -related coronary disease, the A2756G polymorphism was found to infl uence the risk for breast and colorectal cancer (50,56,77). MTR 2756GG genotype is an inherited vascular risk factor in the pathogenesis of sudden sensorineural hearing loss (26). Maternal polymorphisms in the MTR gene may put the fetus at increased risk for birth defects, such as spina bifi da; heart defects and preterm delivery (18,87,88).…”