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

Kotaro Ogawa, Tatsusada Okuno, Kazuyoshi Hosomichi, Akiko Hosokawa, Jun Hirata, Ken Suzuki, Saori Sakaue, Makoto Kinoshita, Yoshihiro Asano, Katsuichi Miyamoto, Ituro Inoue, Susumu Kusunoki, Yukinori Okada, Hideki Mochizuki

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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-DRB115:01 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-DRB104:05, HLA-B39:01, and HLA-B15:01 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-DRB115:01 (P Conditional = 1.5 × 10-5, OR = 2.91, 95% CI = 1.79-4.72), while HLA-DRB115:01 was just significant when conditioned on HLA-DQβ1 Phe9 (P Conditional = 0.037). Regarding a case-control analysis for NMOSD, HLA-DQA105:03 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.

Original languageEnglish
Article number162
JournalJournal of Neuroinflammation
Volume16
Issue number1
DOIs
StatePublished - 5 Aug 2019
Externally publishedYes

Keywords

  • HLA
  • Multiple sclerosis
  • Neuromyelitis optica spectrum disorder
  • Next-generation sequencing

Fingerprint

Dive into the research topics of 'Next-generation sequencing identifies contribution of both class i and II HLA genes on susceptibility of multiple sclerosis in Japanese'. Together they form a unique fingerprint.

Cite this