The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis

Objective. To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors invo lved in psoriatic arthritis (PsA). Methods. DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequ ence-specific oligonucleotide probes to determine HLA-C, To examine,whether MICA (class I major histocompatibility complex chain-related gene A) confe rs additional susceptibility, trinucleotide repeat polymorphism in the tran smembrane region of the MICA gene was investigated by radioactive PCR, Furt her analysis of MICA was made by PCR-single-strand conformational polymorph ism to determine the allelic variant corresponding to MICA transmembrane po lymorphism. Results, Our results reveal new findings: 1) the frequency of the Cw*0602 a llele was significantly increased in both patient groups: psoriasis (correc ted P [P-corr] < 10(-5), relative risk [RR] 6.2), PsA (P-corr < 10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a sig nificantly higher frequency in PsA patients (P-corr < 0.00035, RR 3.2), whe reas a similar distribution was found in both the control and psoriasis pop ulation, 3) this polymorphism corresponds to the MICA-002 allele and was fo und to be overrepresented in patients with the polyarticular form (P-corr < 0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independen t of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributab le to 1 allele when the relative risk is >1) in PsA patients who carry Cw*0 602. Conclusion, The data obtained in this study are consistent with the polygen ic inheritance of psoriasis, Cw*0602 appears to be the stronger genetic sus ceptibility factor for psoriasis, Independent of the HLA-C association, MIC A-A9 polymorphism corresponding to the MICA-002 allele is a possible candid ate gene for the development of PsA.