High-risk Allele for Herpes Labialis Severity at the IFNL3/4 Locus is Associated With Vestibular Neuritis

Objective: Vestibular neuritis (VN) is a peripheral vestibular disorder leading to a sudden loss of unilateral vestibular function. Although the underlying etiological mechanisms for disease development are not yet known, there is evidence that a latent infection with herpes simplex virus type 1 (HSV-1) might be involved. The polymorphism rs12979860 has been associated with the severity of recurrent herpes labialis and hepatitis C virus (HCV) clearance and treatment outcome and is located within the first intron of the IFNL4 gene on chromosome 19.q13.2. This case control study was conducted to evaluate the association of rs12979860 with VN occurrence. Methods: DNA was extracted from EDTA blood of 151 VN patients and 1,775 healthy controls. Genotyping of rs12979860 was performed using iPLEX and MassARRAY Matrix Assisted Laser Desorption Ionization—Time of Flight (MALDI-TOF) mass spectrometry. For association analyses, an additive, dominant and recessive logistic regression model was calculated, using age and sex as covariates. Results: A significant association of rs12979860 with VN was obtained for the additive [OR = 1.51 (1.18–1.92); p = 9.23 × 10−4] and dominant models [OR = 2.15 (1.48–3.13); p = 5.86 × 10−5], with the T allele being more frequent in the VN group. Conclusion: By detecting a significant association of the rs12979860-T risk allele for herpes labialis severity with susceptibility to VN, this study gives further indirect evidence for an involvement of HSV-1 in VN pathology, thereby strengthening the virus hypothesis

Genome-Wide Association Study in Vestibular Neuritis: Involvement of the Host Factor for HSV-1 Replication

Objective: In order to identify genetic variants associated with vestibular neuritis, a common cause of peripheral vertigo with a potential causative link to the reactivation of herpes simplex type 1 (HSV-1), we conducted a genome-wide association study.Methods: Association was assessed using approximately 8 million variants. 131 patients with vestibular neuritis and 2,609 controls of European ancestry were included.Results: Genome-wide associations with vestibular neuritis were detected in 4 regions containing protein coding genes assignable to two functional groups: virus hypothesis and insulin metabolism. Genes of set 1 are related to viral processes: 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. Ankyrin repeat domain 30A (ANKRD30A) encodes a host factor for human immunodeficiency virus-1 (HIV-1) infection. It shows rapid evolution and is induced by interferon stimulation. Mediator complex 30 (MED30), an important member of the mediator complex, has been shown to be involved in replication of HIV-1, a knockdown leading to impaired viral replication. The second set of genes LIM homeobox transcription factor 1 alpha (LMX1A), solute carrier family 30 member 8 (SLC30A8) is associated with insulin metabolism and resistance, a feature of some patients in whom type 2 diabetes is an accompanying comorbidity of vestibular neuritis.Conclusions: Using a GWAS approach to evaluate the etiology of vestibular neuritis these findings provide another piece of evidence that it may be caused by a viral inflammation

Genome-Wide Association Study in Vestibular Neuritis: Involvement of the Host Factor for HSV-1 Replication

Objective: In order to identify genetic variants associated with vestibular neuritis, a common cause of peripheral vertigo with a potential causative link to the reactivation of herpes simplex type 1 (HSV-1), we conducted a genome-wide association study. Methods: Association was assessed using approximately 8 million variants. 131 patients with vestibular neuritis and 2,609 controls of European ancestry were included. Results: Genome-wide associations with vestibular neuritis were detected in 4 regions containing protein coding genes assignable to two functional groups: virus hypothesis and insulin metabolism. Genes of set 1 are related to viral processes: 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. Ankyrin repeat domain 30A (ANKRD30A) encodes a host factor for human immunodeficiency virus-1 (HIV-1) infection. It shows rapid evolution and is induced by interferon stimulation. Mediator complex 30 (MED30), an important member of the mediator complex, has been shown to be involved in replication of HIV-1, a knockdown leading to impaired viral replication. The second set of genes LIM homeobox transcription factor 1 alpha(LMX1A), solute carrier family 30 member 8 (SLC30A8) is associated with insulin metabolism and resistance, a feature of some patients in whom type 2 diabetes is an accompanying comorbidity of vestibular neuritis. Conclusions: Using a GWAS approach to evaluate the etiology of vestibular neuritis these findings provide another piece of evidence that it may be caused by a viral inflammation