Genetic and acquired prothrombotic risk factors and sudden hearing loss

Idiopathic sudden sensorineural hearing loss (ISSNHL) is a frequently encountered condition, and various pathogenetic mechanisms have been hypothesized, such as viral infections, autoimmune processes, and ischemic events; however, whatever the cause, impaired cochlear perfusion appears to be the most important event. A number of inherited prothrombotic risk factors and their related genetic alterations have recently been correlated with vascular disorders.

To investigate the mechanisms of vascular thrombosis of the inner ear leading to sudden HL, we examined 100 patients with SSNHL for the presence of acquired or inherited prothrombotic risk factors and 200 healthy volunteers as controls. All of the subjects underwent hematologic examinations, including MTHFR C677T and A1298C, prothrombin G20210A, platelet GlyIIIaA1/A2, V Leiden G1691A genotyping, fibrinogenemia, cholesterolemia, homocystinemia, and folatemia. Genomic DNA was isolated from peripheral blood leukocytes using standard methods, and gene mutations were investigated using a LightCycler DNA analyser and polymerase chain reaction.

A statistically significant association was found between SSNHL and the MTHFR C677T/A1298C polymorphisms, the prothrombin G20210A transition, and the platelet GlyIIIa and V Leiden G1691A mutations. Furthermore, the SSNHL patients had significantly higher levels of fibrinogenemia, cholesterolemia, and homocystinemia and lower levels of folatemia than the controls (P < .0001).

The association between inherited and acquired prothrombotic factors and sudden HL suggests that the microvascular impairment causing SSNHL may be caused by a multifactorial mechanism. All patients with ISSNHL should undergo a comprehensive hematologic investigation of inherited and acquired prothrombotic factors, including MTHFR polymorphisms, the prothrombin transition, and the platelet and V Leiden mutations, to identify a subset of patients at high risk of recurrent HL.