Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis [Metaanalyse des Zusammenhangs zwischen funktionell wirksamen MICA-TM-Polymorphismen und systemisch

Abstract

ObjectiveThe 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).MethodsA 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.ResultsA 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 (pcorrected?=?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?×?10?7) but not in Europeans; the association in Asians remained significant after Bonferroni correction (pcorrected?=?4.5?×?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?×?10?9 and OR =?9.461, 95?% CI =?5.754?15.55, p?<?1.0?×?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 (pcorrected?=?0.245).ConclusionThis 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.