Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and *0901.
OBJECTIVE
To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population.


METHODS
All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons.


RESULTS
The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 x 10(-24), odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 x 10(-9), OR 2.47 [95% CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/*0901 was associated with the highest risk of RA (corrected P = 1.81 x 10(-11), OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was approximately 4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus 84.3%, OR 2.33 [95% CI 1.24-4.39]).


CONCLUSIONS
The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.
Lee
Hye-Soon
HS
Hanyang University College of Medicine, Hospital for Rheumatic Diseases, University Medical Center, Seoul 133-792, South Korea.
Lee
Kyung Wha
KW
Song
Gwan Gyu
GG
Kim
Hyun-Ah
HA
Kim
Shin-Yoon
SY
Bae
Sang-Cheol
SC
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C493960:HLA-DRB1*04:05 antigen; C487381:HLA-DRB1*09:01 antigen