Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis

Abstract

The aim of this study was to determine whether the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism is associated with susceptibility to systemic lupus erythematous (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). A meta-analysis was conducted to establish the association between MICA-TM polymorphisms and SLE, RA and AS in the overall study population, as well as in each ethnic group. A total of 13 comparison studies, including five SLE (1601 patients; 1846 controls), four RA (701 patients; 887 controls) and four AS (346 patients; 356 controls) studies were considered in the meta-analysis. An association between the MICA-TM A5.1 allele and SLE was demonstrated in Europeans but not in Asians: odds ratio (OR) = 1.699, 95 % confidence interval (CI) = 1.123-2.569, p = 0.012 and OR = 0.949, 95 % CI = 0.502-1.793, p = 0.871, respectively. However, no association was found in Europeans after Bonferroni correction (p(corrected) = 0.060). An association was found between the MICA-TM A9 allele and RA in Asians (OR = 0.527, 95 % CI = 0.408-0.681, p = 8.9 x 10(-7)) but not in Europeans; the association in Asians remained significant after Bonferroni correction (p(corrected) = 4.5 x 10(-6)). An association between the MICA-TM A4 phenotype and AS was observed in European and Asian populations (OR = 12.87, 95 % CI = 6.747-24.58, p < 1.0 x 10(-9) and OR = 9.461, 95 % CI = 5.754-15.55, p < 1.0 x 10(-9), respectively). Meta-analysis stratified by human leukocyte antigen (HLA)-B27 status revealed an association between the MICA-TM A4 phenotype and HLA-B27 positivity AS in Asians, but not in Europeans (OR = 0.318, 95 % CI = 0.102-0.995, p = 0.049 and OR = 2.080, 95 % CI = 0.422-10.25, p = 0.368, respectively). However, the association in Asians was not significant after Bonferroni correction (p(corrected) = 0.245). This meta-analysis demonstrated that there was no association between MICA-TM polymorphisms and SLE susceptibility, but that the MICA-TM A9 allele was associated with an RA risk in Asians. Moreover, the association between the MICA-TM A4 phenotype and AS was HLA-B27-dependent.