MICA-STR A.4 is associated with slower hearing loss progression in patients with Ménière's disease.
OBJECTIVE
Immune response may influence hearing outcome in Ménière's disease (MD).


BACKGROUND
Major histocompatibility complex class I chain-related A (MICA) encodes a highly polymorphic stress-inducible protein, which interacts with NKGD2 receptor on the surface of NK, γδ T cells and T CD8 lymphocytes. We investigated the association of MICA gene with hearing outcome in MD and its linkage disequilibrium (LD) with human leukocyte antigen (HLA)-B.


METHODS
MICA short tandem repeat polymorphism (MICA-STR) was genotyped using a polymerase chain reaction-based method in a total of 302 Spanish patients with MD and 420 healthy controls. Genotyping of HLA-B was performed using polymerase chain reaction and detected with reverse sequence-specific oligonucleotide probe system in 292 patients and 1,014 controls.


RESULTS
Hearing loss was associated with the duration of MD (p = 0.001). We found that MICA*A5 alelle was significantly associated in the Mediterranean set (Pc = 0.04, odds ratio = 0.51 [95% confidence interval, 0.30-0.84]), but this finding was not replicated in the Galicia population. However, median time to develop hearing loss greater than 40 dB was 16 years (95% confidence interval, 9-23) for patients with the MICA*A.4 allele and 10 years (95% confidence interval, 9-11) for patients with another MICA-STR allele (log-rank test, p = 0.0038). We did not find statistical differences in the distribution of B locus between the MD and the control group. In the LD analysis, MICA*A5.1-HLA-B*07 (8.8%), MICA*A6-HLA-B*44 (8.3%), and MICA*A6-HLA-B*51 (8.3%) were the most common haplotypes, and the stronger LD was found for haplotypes MICA*A.4-HLA-B*18 (r2 = 0.41) and MICA*A.4-HLA-B*27(r2 = 0.29).


CONCLUSIONS
The allelic variant MICA*A.4 is significantly associated with slower progression of hearing loss in patients with MD. This suggests that the immune response influence hearing level in MD.
Otology and Neurotology Group CTS495, GENYO, Centro de Genómica e Investigación Oncológica-Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain.
Irene
I
Gazquez
Antonia
A
Moreno
Ismael
I
Aran
Andres
A
Soto-Varela
Sofia
S
Santos
Herminio
H
Perez-Garrigues
Alicia
A
Lopez-Nevot
Teresa
T
Requena
Miguel Angel
MA
Lopez-Nevot
Jose Antonio
JA
Lopez-Escamez
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D034381:Hearing Loss / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008297:Male; D008575:Meniere Disease / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012008:Recurrence; D013030:Spain / Q000453:epidemiology; D016019:Survival Analysis; D055815:Young Adult
D017931:DNA Primers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D004247:DNA