• Methylenetetrahydrofolate reductase;
  • polymorphism;
  • sudden hearing loss;
  • nested case-control study;
  • Level of Evidence: 2b.



To investigate the recently reported association of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with sudden sensorineural hearing loss (SSNHL), we analyzed data from a community-based Japanese population.

Study Design:

Nested case-control study.


Among 2,174 adults (1,096 males and 1,078 females) aged 40 to 79 years old who participated in the National Institute for Longevity Sciences–Longitudinal Study of Aging, we compared 33 cases of prevalent SSNHL, defined as a self-reported otolaryngologist diagnosis, with the other cases. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with the MTHFR C677T polymorphism, with adjustment for other possibly influential factors under additive, dominant, and recessive genetic models.


The per-allele ORs for SSNHL risk were 1.687 (95% confidence interval [CI], 1.023–2.780) in model 1, with adjustment for age and sex, and 1.654 (CI, 1.003–2.728) in model 2, with adjustment for smoking status, body mass index, histories of heart disease, hypertension, and diabetes, in addition to the factors in model 1. In model 3, a significant association between SSNHL and the C677T polymorphism was observed under all genetic models independent of factors including folic acid and homocysteine, although there were only 25 cases and 1,677 controls due to the addition of moderating factors.


Our results suggest that the T allele of MTHFR C677T could be associated with susceptibility to SSNHL, and even imply that this mutation could be a risk factor that is independent of blood folic acid and homocysteine. Laryngoscope, 2010