Methylenetetrahydrofolate reductase gene mutations as risk factors for sudden hearing loss.

Sudden hearing loss (SHL) can be caused by vascular disorders favoring impaired cochlear perfusion. Several inherited prothrombotic risk factors have been considered in the pathogenesis of vascular impairment, and the possible role of genetic alterations has recently been suggested. Methylenetetrahydrofolate reductase (MTHFR) gene mutations at nucleotides 677 and 1298 cause reduced MTHFR enzyme activity, which leads to increased homocysteine and reduced serum folate levels that are known to be involved in vascular impairment. We studied the relationship between SHL and MTHFR C677T and A1298C gene polymorphisms in 67 patients with SHL and 134 controls. Wild-type MTHFR CC677/AA1298 was significantly more frequent in the controls (P = .05), and gene mutations were significantly more frequent in the patients (P = .001; P = .001 for trend). Fifty-three patients (79.1%) and 56 controls (41.8%) (P = .012) had a double mutation (homozygosis 677TT or 1298CC; compound heterozygosis for both polymorphisms). Homocysteine levels were significantly higher and serum folate levels significantly lower in the patients than in the controls (P < .0001). These data suggest that MTHFR gene polymorphisms may be involved in the pathogenesis of SHL.