Major Histocompatibility Complex Class I Chain-Related Gene Polymorphisms: Associated with Susceptibility to Kawasaki Disease and Coronary Artery Aneurysms

Abstract

Background: Kawasaki disease (KD) involves a complex interaction of immunoinflammatory process, cytokine activation, and genetic factors. We aimed to investigate whether genetic variations in a major histocompatibility complex (MHC) class could be used as markers of susceptibility in KD and coronary artery aneurysm lesions (CALs). Methods: Individuals were divided into following groups: (1) normal controls; (2) KD with CAL; (3) KD without CAL. Polymorphisms for MHC class I chain-related genes A (MICA) (rs2301747, rs2256184, rs2848716), MICB (rs2855804, rs3132464, rs2516400), BAT3 (rs750332), MSH5 (rs1150793), and chromosome 6 open reading frame 27 (C6orf27, rs707928) were genotyped with polymerase chain reaction and the TaqMan^® allelic discrimination assay. Genotypes, alleles, and haplotype in each group were compared. Results: Genotype and allele frequency of MICB*rs2516400 polymorphisms in each group were significantly different. MICB (rs2516400)*C-related genotypes/alleles are correlated with development of KD and CAL. Proportions of rs2516400*TT/TC/CC were (1) 1/39/60%, (2) 0/0/100%, and (3) 0/0/100%. Other single-nucleotide polymorphisms were not associated with KD susceptibilities. Haplotypes (rs2301747-rs2256184-rs2848716-rs2855804-rs3132464-rs2516400-rs750332-rs1150793-rs707928) G-G-G-C-T-C-T-A-A, C-A-G-T-T-C-T-A-A, and G-G-G-C-C-C-T-A-A were associated with higher susceptibilities for KD. The G-G-G-T-T-T-T-G-G and C-G-G-T-T-T-T-A-A haplotypes were associated with lower susceptibilities. Conclusion: MICB*rs2516400 polymorphisms and some MHC class I-related haplotypes are associated with KD susceptibility. MICB and MHC class I genetic variations might contribute to the pathogenesis of KD and CAL.