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

Journal of Neuroinflammation

卷:16

Kazuyoshi Hosomichi¹  Yoshihiro Asano²  Susumu Kusunoki³  Katsuichi Miyamoto³  Tatsusada Okuno⁴  Hideki Mochizuki⁴  Makoto Kinoshita⁴  Akiko Hosokawa⁴  Saori Sakaue⁵  Kotaro Ogawa⁵  Yukinori Okada⁵  Jun Hirata⁵  Ken Suzuki⁵  Ituro Inoue⁶ 

[1] Department of Bioinformatics and Genomics Graduate School of Advanced Preventive Medical Sciences, Kanazawa University;

[2] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine;

[3] Department of Neurology, Kindai University Faculty of Medicine;

[4] Department of Neurology, Osaka University Graduate School of Medicine;

[5] Department of Statistical Genetics, Osaka University Graduate School of Medicine;

[6] Division of Human Genetics, National Institute of Genetics;

关键词: Multiple sclerosis;    Neuromyelitis optica spectrum disorder;    HLA;    Next-generation sequencing;   

DOI  :  10.1186/s12974-019-1551-z

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown