Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population

The aim of this study was to examine whether the association of psoriatic a rthritis (PsA) with human leukocyte antigen (HLA) class I genes is secondar y to linkage disequilibrium with a nearby gene. We examined a sample of the Jewish population to investigate whether HLA-B/C and DR polymorphism is as sociated with:susceptibility, or whether other closely related class I loci , such as the major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor (TNF), might play a role in disease devel opment. Comparisons of different populations with different HLA profiles wo uld be of value in identifying the candidate genes involved in PSA. Fifty t wo patients with PsA and 73 random: matched controls from a Jewish populati on were selected and DNA typed by polymerase chain reaction-single-strand o ligonucleotide probe (PCR-SSOP) (HLA-C), PCR sequence-specific primers (PCR -SSP) (HLA-B, DR), radioactive PCR (MICA-TM polymorphism in the transmembra ne region), and PCR-RFLP (TNF). Some findings can be concluded from the stu dy: (1) the frequency of HLA-B*5701, B*3801, B*39, B*27, Cw*0602, Cw*07, DR B1*0402, and DRB1*0701 were not found to be significantly increased in PsA; (2) no significant differences of TNF alpha' promoter alleles at positions -308 and -238 were found between PsA and healthy controls; (3) the trinucl eotide repeat polymorphism MICA-A3 was present at a higher frequency in PsA patients, (p, < 0.009, RR = 3.34, EF = 0.39); and (4) MICA-A9 polymorphism was found in linkage disequilibrium with HLA-B alleles (B*5701, B*3801) de scribed to be associated with PsA in Caucasians. These results suggest that the MICA gene or other nearby gene(s) may be involved in the development o f PsA, and it would thus appear that psoriasis vulgaris (PsV) and PsA are a ssociated with different MHC susceptibility genes. Human Immunology 62, 632 - 638 (2001). (C) American Society for Histocompatibility and Immunogenetic s, 2001. Published by Elsevier Science Inc.