HETEROZYGOTE CARRYING HLA-DRB1*0405 AND DRB1*0901 IS DISADVANTAGEOUS IN SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN THE KOREAN POPULATION.

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HETEROZYGOTE CARRYING HLA-DRB1*0405 AND DRB1*0901 IS DISADVANTAGEOUS IN SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN THE KOREAN POPULATION.
Kyung Wha Lee, PhD, Hye-Soon Lee, MD, PhD, Gwan Gyu Song, MD, PhD and Sang-Cheol Bae, MD, PhD. Anyang Kyungki-Do, Korea, Hallym University, 431-070, Hallym Institute for Genome Application; Seoul Korea, College of Medicine, Hanyang University, Internal Medicine and Seoul Korea, College of Medicine, Korea University, Internal Medicine.

Objectives: This study investigated the association of susceptible and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and the following clinical markers: sex, age at disease onset, seropositivity, and disease severity. Methods: Patients with RA (n = 574) and controls of the same ethnic background (n = 392) were included in this study. HLA-DRB1 allele types were identified by PCR-SBT. Results: The DRB1*0405 and DRB1*0901 alleles showed a significantly increased frequency in patients with RA (P = 7.83X10^-24, OR 4.40 [95% CI 3.24–5.99], and P = 2.71X10^-5, OR 1.90 [95% CI 1.40–2.58], respectively). Several alleles (DRB1*0403, 0406, 0701, 0802, 1101, 1202, 1301, 1302, 1403, and 1405) showed significant protective effects (Pc = 9.24X10^-14, OR 0.43). Both of susceptible and protective alleles showed a gene dosage effect, and were each associated with RA independently of the other. The compound heterozygote DRB1*0405/0901 was associated with the highest risk for RA (Pc = 1.81X10^-11, OR 58.2 [95% CI 7.95–425.70]). The age at disease onset was significantly lower in patients with at least one copy of DRB1*0405 (P = 0.003, 36.4 ± 11.7 vs 39.8 ± 12.3 years) and DRB1*0901 (P = 0.035, 37.1 ± 11.5 vs 39.8 ± 12.3 years). Radiographic changes (stages 2–4) were more frequent only in patients with at least one copy of DRB1*0405. Conclusion: These data suggest that DRB1*0405 and DRB1*0901 alleles are risk factors on RA susceptibility and a heterozygote carrying both alleles is obviously disadvantageous to RA in the Korean population.