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MICA-STR A.4 is associated with slower hearing loss progression in patients with Ménière's disease
Irene Gazquez1, Antonia Moreno, Ismael Aran
1Otology and Neurotology Group CTS495, GENYO, Centro de Genómica e Investigación Oncológica-Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain.
Hypothesis:
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).
Conclusion:
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.
Insights
The MICA*A.4 allele is linked to slower hearing loss progression in Ménière
Area of Science:
- Immunogenetics
- Otolaryngology
- Human Genetics
Background:
- Ménière's disease (MD) hearing outcomes may be influenced by immune responses.
- Major histocompatibility complex class I chain-related A (MICA) is a polymorphic gene interacting with immune receptors.
- Investigated MICA gene association with hearing loss in MD and linkage disequilibrium with human leukocyte antigen (HLA)-B.
Purpose of the Study:
- To investigate the association between MICA gene polymorphisms and hearing outcomes in patients with Ménière's disease (MD).
- To examine the linkage disequilibrium (LD) between MICA and human leukocyte antigen (HLA)-B.
Main Methods:
- Genotyped MICA short tandem repeat polymorphism (MICA-STR) in 302 Spanish MD patients and 420 controls using polymerase chain reaction.
- Genotyped HLA-B in 292 MD patients and 1,014 controls via polymerase chain reaction and reverse sequence-specific oligonucleotide probe system.
Main Results:
- Hearing loss in MD correlated with disease duration (p = 0.001).
- The MICA*A5 allele showed association in the Mediterranean cohort (Pc = 0.04) but not in Galicia.
- Patients with MICA*A.4 allele had a median of 16 years to develop >40 dB hearing loss, versus 10 years for other MICA-STR alleles (log-rank test, p = 0.0038).
- No significant differences in HLA-B locus distribution between MD patients and controls.
- Stronger LD observed for MICA*A.4-HLA-B*18 (r2 = 0.41) and MICA*A.4-HLA-B*27 (r2 = 0.29) haplotypes.
Conclusions:
- The MICA*A.4 allele is significantly associated with a slower rate of hearing loss progression in Ménière's disease.
- This finding supports the hypothesis that immune responses influence hearing levels in MD.
