A POLYMORPHIC GENE FAMILY CALLED THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS 1 CHAIN RELATED GENE A

C. Butt, D. Hallett, M. Uddin, P. RahmanRheumatology, Memorial University of Newfoundland, St. John's Rheumatology, University of Toronto, Toronto, CanadaObjectives: The MICA (major histocompatibility complex class I-related chain A) gene is a highly polymorphic gene in the HLA Class I region. Microsatellite repeats in the transmembrane region of exon 5 of the MICA gene has been associated with PsA in several studies. MICA-9 allele was the most consistently associated allele. However the sample size for these studies were small, the levels of significance marginal and the results were occasionally conflicting. As a result we set out to examine common MICA alleles in a well defined PsA cohort. A meta-analysis of the strongest associated MICA allele (MICA A-9) was then conducted. Methods: We assessed 309 Caucasian PsA patients and 310 ethnically matched controls for the exon 5 repeat polymorphism. The alleles were assessed using the Beckman Coulter CEQ 8000 automatic sequencer. We then performed a meta-analysis of MICA alleles and PsA using previously reported data. Results: For the MICA-A9 allele there were 102/309 PsA patients vs 71/310 controls [OR 1.66 (1.2 – 2.4) p-value 0.005]; for MICA-A6 it was 79/309 vs 101/310 [OR 0.71 (0.50-1.0) p =0.05]; for MICA-A5.1 it was 226/309 vs 218/310 [OR 1.14 (0.8-1.60 p=0.43]; for MICA-A5 it was 51/309 vs 72/310 [OR 0.65 (0.44-0.97) p=0.04] and for MICA-A4 it was 72/309 vs 59/310 [OR 1.29 (0.9-1.9) p=0.19] respectively. Only the MICA A-9 allele was significant after correction for multiple testing. A total of six studies met the inclusion criteria for the meta-analysis. This included 884 PsA cases and 1023 controls genotyped for the MICA A-9 allele. The overall OR and 95%CI for the association in the meta-analysis between PsA and MICA A9 was 1.89 (1.55, 2.31; p < 0.0001). There was no significant heterogeneity between these studies. Please see figure. Conclusion: Our meta-analysis confirms the association of MICA-A9 allele and PsA. Disclosure of Interest: None declaredCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 184Session: Genomics, genetic basis of disease and HLA/T cell recognition (Poster Presentations )