Next-generation sequencing identifies contribution of both class I and II HLA genes on susceptibility of multiple sclerosis in Japanese.

Autor: Ogawa K; Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan.; Department of Neurology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan., Okuno T; Department of Neurology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan., Hosomichi K; Department of Bioinformatics and Genomics Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, 920-8640, Japan., Hosokawa A; Department of Neurology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.; Department of Neurology, Suita Municipal Hospital, Suita, 564-8567, Japan., Hirata J; Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan.; Pharmaceutical Discovery Research Laboratories, Teijin Pharma Limited, Hino, 191-8512, Japan., Suzuki K; Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan., Sakaue S; Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan., Kinoshita M; Department of Neurology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan., Asano Y; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan., Miyamoto K; Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, 589-8511, Japan., Inoue I; Division of Human Genetics, National Institute of Genetics, Shizuoka, 411-8540, Japan., Kusunoki S; Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, 589-8511, Japan., Okada Y; Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan. yokada@sg.med.osaka-u.ac.jp.; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, 565-0871, Japan. yokada@sg.med.osaka-u.ac.jp., Mochizuki H; Department of Neurology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2019 Aug 05; Vol. 16 (1), pp. 162. Date of Electronic Publication: 2019 Aug 05.
DOI: 10.1186/s12974-019-1551-z
Abstrakt: Background: The spectrum of classical and non-classical HLA genes related to the risk of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in the Japanese population has not been studied in detail. We conducted a case-control analysis of classical and non-classical HLA genes.
Methods: We used next-generation sequencing (NGS)-based HLA genotyping methods for mapping risk for 45 MS patients, 31 NMOSD patients, and 429 healthy controls. We evaluated the association of the HLA variants with the risk of MS and NMOSD using logistic regression analysis and Fisher's exact test.
Results: We confirmed that HLA-DRB1*15:01 showed the strongest association with MS (P = 2.1 × 10 -5 ; odds ratio [OR] = 3.44, 95% confidence interval [95% CI] = 1.95-6.07). Stepwise conditional analysis identified HLA-DRB1*04:05, HLA-B*39:01, and HLA-B*15:01 as being associated with independent MS susceptibility (P Conditional  < 8.3 × 10 -4 ). With respect to amino acid polymorphisms in HLA genes, we found that phenylalanine at HLA-DQβ1 position 9 had the strongest effect on MS susceptibility (P = 3.7 × 10 -8 , OR = 3.48, 95% CI = 2.23-5.43). MS risk at HLA-DQβ1 Phe9 was independent of HLA-DRB1*15:01 (P Conditional  = 1.5 × 10 -5 , OR = 2.91, 95% CI = 1.79-4.72), while HLA-DRB1*15:01 was just significant when conditioned on HLA-DQβ1 Phe9 (P Conditional  = 0.037). Regarding a case-control analysis for NMOSD, HLA-DQA1*05:03 had a significant association with NMOSD (P = 1.5 × 10 -4 , OR = 6.96, 95% CI = 2.55-19.0).
Conclusions: We identified HLA variants associated with the risk of MS and NMOSD. Our study contributes to the understanding of the genetic architecture of MS and NMOSD in the Japanese population.
Databáze: MEDLINE
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