LAUSR

Background Virus infections affecting the central nervous system are discussed as causative risk factors for a variety of conditions, among those diseases as diverse as Alzheimer's disease and vestibular neuritis. Vestibular neuritis is the third most common cause of peripheral vertigo and is characterized by an acute onset of sustained spinning vertigo, lasting for many days. Although there is indirect evidence that it may be caused by the reactivation of Herpes Simplex Type 1 (HSV-1), its etiology is largely unknown. Methods A genome-wide association study approach was used, including 131 patients with vestibular neuritis and 2609 healthy controls. Results Genome-wide associations with vestibular neuritis were detected in 5 regions containing protein coding genes assignable to two functional groups: virus hypothesis and insulin metabolism. Genes of set 1 are related to viral processes: 1) Nuclear receptor subfamily 3 group C member 2 (NR3C2) is a receptor for mineralocorticoids and glucocorticoids and was shown to be a host factor for HSV-1 replication. 2) Ankyrin repeat domain-containing protein 30 A (ANKRD30A) is a host factor for human immunodeficiency virus-1 (HIV-1) infection. It shows rapid evolution and is induced by interferon stimulation. 3) Mediator of RNA polymerase II transcription subunit 30 (MED30) is an essential member of the mediator and has been shown to be involved in replication of HIV-1, a knockdown leading to impaired viral replication. The second set of genes (LMX1 A, SLC30A8, HTR2C) is associated to insulin metabolism and resistance, a feature of some patients with type 2 diabetes as an accompanying comorbidity of VN. Discussion Using a GWAS approach to evaluate the etiology of vestibular neuritis these findings give another piece of evidence that it may be caused by a viral inflammation. Apart from replication of these results in larger cohorts a closer look at a possible genetic and phenotypic overlap between HSV-1 induced diseases is necessary.