Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four Independent Protective Alleles, DRB113:02, DRB114:06, DQB103:01, and DPB102:01

• Published in: PloS one Vol. 11; no. 4; p. e0154255
• Main Authors: Furukawa, Hiroshi, Oka, Shomi, Kawasaki, Aya, Shimada, Kota, Sugii, Shoji, Matsushita, Takashi, Hashimoto, Atsushi, Komiya, Akiko, Fukui, Naoshi, Kobayashi, Kouji, Osada, Atsumu, Ihata, Atsushi, Kondo, Yuya, Nagai, Tatsuo, Setoguchi, Keigo, Okamoto, Akiko, Okamoto, Akira, Chiba, Noriyuki, Suematsu, Eiichi, Kono, Hajime, Katayama, Masao, Hirohata, Shunsei, Sumida, Takayuki, Migita, Kiyoshi, Hasegawa, Minoru, Fujimoto, Manabu, Sato, Shinichi, Nagaoka, Shouhei, Takehara, Kazuhiko, Tohma, Shigeto, Tsuchiya, Naoyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.04.2016; Public Library of Science (PLoS)
• Subjects: Adult; Alleles; Analysis; Antibodies; Antigens; Asian Continental Ancestry Group - genetics; Autoantibodies; Autoimmune diseases; Biology and Life Sciences; Confidence intervals; Contingency tables; Dermatology; Development and progression; DNA topoisomerase; Drb1 protein; Engineering and Technology; Epidemiology; Female; Gene frequency; Genetic aspects; Genetic Predisposition to Disease; Health sciences; Histocompatibility antigen HLA; HLA antigens; HLA-DP beta-Chains - genetics; HLA-DQ beta-Chains - genetics; HLA-DRB1 Chains - genetics; Hospitals; Humans; Immunoglobulins; Infectious diseases; Internal medicine; Japan - epidemiology; Laboratories; Leukocytes; Lupus; Male; Medicine; Medicine and Health Sciences; Middle Aged; Patients; Physical Sciences; Physiological aspects; Protective Factors; Research and Analysis Methods; Rheumatic diseases; Rheumatoid arthritis; Rheumatology; Risk factors; Scleroderma; Scleroderma (Disease); Scleroderma, Systemic - epidemiology; Scleroderma, Systemic - genetics; Systemic sclerosis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154255

Several studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic sclerosis (SSc) have been reported. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are found in SSc patients. Here, we sought to identify HLA alleles associated with SSc in Japanese, and explored their associations with SSc phenotypes including the presence of autoantibodies. Associations of HLA-DRB1, DQB1, and DPB1 were analyzed in 463 Japanese SSc patients and 413 controls. We found that DRB1*13:02 (P = 0.0011, Pc = 0.0319, odds ratio [OR] 0.46, 95% confidence interval [CI] 0.29-0.73), DRB1*14:06 (P = 6.60X10-5, Pc = 0.0020, OR 0.05, 95%CI 0.01-0.41), DQB1*03:01 (P = 0.0009, Pc = 0.0150, OR 0.56, 95%CI 0.40-0.79), and DPB1*02:01 (P = 5.16X10-6, Pc = 8.77X10-5, OR 0.52, 95%CI 0.39-0.69) were protectively associated with SSc. In addition, these four alleles seemed to be independently associated with the protection against the susceptibility of SSc. On the other hand, we could not find predisposing alleles for overall SSc. With respect to SSc subsets, a tendency for these four alleles to be protectively associated was observed. However, there was a significant association between DRB1*01:01, DRB1*10:01, DQB1*05:01, and DPB1*04:02 and the susceptibility to SSc with ACA. On the other hand, the presence of DRB1*15:02, DQB1*06:01, DPB1*03:01, and DPB1*09:01 was associated with SSc with ATA. Thus, the present study has identified protective associations of the four HLA class II alleles with overall Japanese SSc and predisposing associations of HLA class II alleles with Japanese SSc subsets.