Variants at HLA-A, HLA-C, and HLA-DQB1 confer risk of psoriasis vulgaris in Japanese.

4 years ago

Variants at HLA-A, HLA-C, and HLA-DQB1 confer risk of psoriasis vulgaris in Japanese.

Takeshi Ozeki, Mayumi Tamari, Nobuyuki Hizawa, Hidemi Nakagawa, Takeaki Sudo, Yukinori Okada, Masahiro Kanai, Hidehisa Saeki, Shinichi Sato, Toshihiro Tanaka, Taisei Mushiroda, Jun Hirata, Tomomitsu Hirota

Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiological and genetic landscapes of global populations. We conducted an initial genome-wide association study (GWAS) and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the SNPs with PsV risk at TNIP1 and the MHC region (P = 3.7×10(-10) and 6.6×10(-15), respectively). By updating the HLA imputation reference panel of Japanese (n = 908) to expand HLA gene coverage, we fine-mapped the HLA variants associated with PsV risk. While we confirmed PsV risk of HLA-C*06:02 (odds ratio [OR] = 6.36, P = 0.0015), its impact was relatively small compared to those in other populations due to rare allele frequency in Japanese (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most significant association with PsV (OR = 4.61, P = 1.2×10(-10)). In addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified an independent PsV risk of HLA-DQβ1 Asp57 (OR = 2.19, P = 1.9×10(-6)). Our PsV GWAS in Japanese highlighted novel genetic architecture of PsV, including the identification of novel HLA risk variants.

Publisher URL: http://doi.org/10.1016/j.jid.2017.10.001

DOI: 10.1016/j.jid.2017.10.001