Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis.
We examined associations between human leukocyte antigen DRB1 (HLA-DRB1) shared epitope (SE), receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), and interleukin 17 (IL-17) genotypes with age of disease onset and radiographic progression in Japanese patients with early rheumatoid arthritis (RA). HLA-DRB1 genotypes were evaluated in 123 patients with early RA (98 female, 25 male) within 1 year of symptom onset. In 72 patients, radiographic progression over a 2-year period was evaluated using Larsen's methods, and genotypes of three polymorphic sites in RANK, five sites in RANKL, two sites in OPG, and three sites in IL-17 were determined by direct polymerase chain reaction sequencing. Possession of an SE allele was significantly associated with earlier disease onset in females (median 46.9 vs 51.9 years in SE- patients; P = 0.04). Single nucleotide polymorphisms (SNPs) in RANKL (rs2277438, P = 0.028) and IL-17 (rs3804513, P = 0.049) were significantly associated with radiographic progression at 2 years. RANKL-G-, SE- patients (n = 12) had significantly less joint damage than did RANKL-G+, SE- patients (n = 11; P = 0.0038), RANKL-G-, SE+ patients (n = 21; P = 0.0018) and RANKL-G+, SE+ patients (n = 28; P = 0.0024). In Japanese RA patients, HLA-DRB1 SE alleles are associated with disease onset at an earlier age, as has been observed in Caucasian RA patients. In addition, SNPs in RANKL and IL-17 may be associated with radiographic progression in Japanese patients with early RA.
Furuya
Takefumi
T
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan. furuyat@ior.twmu.ac.jp.
Hakoda
Masayuki
M
Department of Nutritional Sciences, Faculty of Human Ecology, Yasuda Women's University, Hiroshima, Japan.
Ichikawa
Naomi
N
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
Higami
Kenshi
K
Higami Hospital, Kashihara, Japan.
Nanke
Yuki
Y
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
Yago
Toru
T
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
Kamatani
Naoyuki
N
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
Kotake
Shigeru
S
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D053245:RANK Ligand / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D012189:Retrospective Studies
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D020381:Interleukin-17; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D004247:DNA