HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data
| Autor: | Yukio Takeshita, Hikoaki Fukaura, Noriko Isobe, Yuko Shimizu, Shoji Tsuji, Katsuhisa Masaki, Kazuhide Ochi, Shin Hisahara, Ryuichi Sakate, Mitsuru Watanabe, Takuya Matsushita, Makoto Matsui, Takahiro Iizuka, Jun Ichi Kira, Susumu Kusunoki, Yuri Nakamura, Ayako Sakoda, Akio Suzumura, Etsuji Saji, Kazumasa Okada, Masanori Mizuno, Tomonori Kimura, Hirofumi Ochi, Kazutoshi Nishiyama, Takashi Kanda, Akiko Nagaishi, Shinya Sato, Masami Tanaka, Tatsusada Okuno, Masaaki Niino, Takanori Yokota, Fumie Hayashi, Izumi Kawachi, Yoichiro Nishida, Ken Yamamoto, Katsuichi Miyamoto, Makoto Hirata, Yuji Nakatsuji, Takashi Ohashi, Shigemi Nagayama, Shun Shimohama, Yuji Kawano, Koji Shinoda |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male musculoskeletal diseases 0301 basic medicine medicine.medical_specialty Multiple Sclerosis Genotype Science Neuroimmunology Human leukocyte antigen Gastroenterology Article 03 medical and health sciences 0302 clinical medicine Japan immune system diseases Internal medicine medicine Humans Optic neuritis skin and connective tissue diseases Genetic Association Studies HLA-DP beta-Chains Genetic association study Biological Specimen Banks Multidisciplinary business.industry Multiple sclerosis Neuromyelitis Optica Case-control study Middle Aged medicine.disease Spinal cord Phenotype 030104 developmental biology medicine.anatomical_structure Neurology Neuromyelitis Optica Spectrum Disorders Case-Control Studies Medicine Female Brainstem business 030217 neurology & neurosurgery HLA-DRB1 Chains |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype–phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype–phenotype correlations are unclear in NMOSD. |
| Databáze: | OpenAIRE |
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