A meta-analysis of the association between Behçet's disease and MICA-A6

Abstract

Abstract. Behçet's disease (BD) is a multi-system inflammatory condition with unknown cause, characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis and skin lesions. It predominantly affects people living around the Mediterranean basin and in Japan. The effects of the major histocompatibility complex class I chain related gene A (MICA) A6 allele on susceptibility to Behçet's disease (BD) have been reported previously, however, their results have been unreliable. The present study aimed to determine whether an association between the MICA-A6 allele and BD susceptibility exists. A total of 12 case-control studies, examining the association between MICA-A6 and BD and involving 752 cases and 1,175 controls were included in the present meta-analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The results of meta-analysis revealed that the frequency of the MICA-A6 allele in the case group was significantly higher than those in the control groups (P<0.001, OR=2.43, 95% CI: 1.99-2.97). Sub-group analysis by ethnicity indicated that the association between of MICA-A6 gene to BD remained in Asian populations (5 cases and 731 controls) and Caucasian populations (242 cases and 444 controls) with OR=2.65, 95% CI: 2.07-3.38 and OR=2.23, 95% CI: 1.37-3.62, respectively. These findings demonstrate that MICA-A6 gene is associated with susceptibility to BD. The MICA-A6 gene may serve as an early diagnostic marker for BD in the future.

Genetics of Behçet’s Disease

“…MICA*009 and *019 alleles were associated with BD in a Spanish population [42], and MICA-A6 allele with Japanese and Korean BD patients [43][44][45]. The latter appeared to be independent from the potential linkage disequilibrium (LD) effect of HLA-B51 according to the Korean study [45].…”

Genetics in Behcet’s Disease: An Update Review

“…A tri-nucleotide microsatellite polymorphism (GCT/AGC) n was identified in the MICA transmembrane region designated as An (A4, A5, A5.1, A6, A9) allele ( 63 ). Among them, MICA-A6 conferred risk to BD while the rest alleles were thought to be protective, especially in the Middle East and East Asia ( 71 , 73 ). MICA*009 and MICA* 019 were identified as risk alleles for BD involving a Spanish population ( 71 , 74 ).…”

Immune Regulatory Genes Are Major Genetic Factors to Behcet Disease: Systematic Review

“…It functions in immune activation under cellular stress conditions, such as infections, tissue injury, pro-inflammatory signals, and malignant transformation. Similar to classic HLA genes, its DNA sequence is highly polymorphic [ 44 ]. According to IMGT/HLA database [ https://www.ebi.ac.uk/ipd/imgt/hla/align.html ], there are more than 100 identified MICA alleles.…”