Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis: A cross-sectional study

yuri nakamura, Takuya Matsushita, Shinya Sato, Masaaki Niino, Toshiyuki Fukazawa, Satoshi Yoshimura, Shin Hisahara, Noriko Isobe, Shun Shimohama, mitsuru watanabe, Kazuto Yoshida, Hideki Houzen, Yusei Miyazaki, Ryo Yamasaki, Seiji Kikuchi, Jun-Ichi Kira

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

Background: Higher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS. Methods: We enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity. Results: The HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p corr =0.0004 and p corr =0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p=0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p=0.0012 and p<0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p=0.0415, p=0.0026, and p<0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p=0.0198). Conclusions: Living at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.

元の言語英語
記事番号239
ジャーナルJournal of Neuroinflammation
13
発行部数1
DOI
出版物ステータス出版済み - 9 6 2016

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HLA Antigens
Multiple Sclerosis
Cross-Sectional Studies
Cerebrospinal Fluid
Immunoglobulin G
Brain
Alleles
Islands
Japan
Population
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

これを引用

Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis : A cross-sectional study. / nakamura, yuri; Matsushita, Takuya; Sato, Shinya; Niino, Masaaki; Fukazawa, Toshiyuki; Yoshimura, Satoshi; Hisahara, Shin; Isobe, Noriko; Shimohama, Shun; watanabe, mitsuru; Yoshida, Kazuto; Houzen, Hideki; Miyazaki, Yusei; Yamasaki, Ryo; Kikuchi, Seiji; Kira, Jun-Ichi.

:: Journal of Neuroinflammation, 巻 13, 番号 1, 239, 06.09.2016.

研究成果: ジャーナルへの寄稿記事

nakamura, yuri ; Matsushita, Takuya ; Sato, Shinya ; Niino, Masaaki ; Fukazawa, Toshiyuki ; Yoshimura, Satoshi ; Hisahara, Shin ; Isobe, Noriko ; Shimohama, Shun ; watanabe, mitsuru ; Yoshida, Kazuto ; Houzen, Hideki ; Miyazaki, Yusei ; Yamasaki, Ryo ; Kikuchi, Seiji ; Kira, Jun-Ichi. / Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis : A cross-sectional study. :: Journal of Neuroinflammation. 2016 ; 巻 13, 番号 1.
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title = "Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis: A cross-sectional study",
abstract = "Background: Higher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS. Methods: We enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity. Results: The HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p corr =0.0004 and p corr =0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p=0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p=0.0012 and p<0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p=0.0415, p=0.0026, and p<0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p=0.0198). Conclusions: Living at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.",
author = "yuri nakamura and Takuya Matsushita and Shinya Sato and Masaaki Niino and Toshiyuki Fukazawa and Satoshi Yoshimura and Shin Hisahara and Noriko Isobe and Shun Shimohama and mitsuru watanabe and Kazuto Yoshida and Hideki Houzen and Yusei Miyazaki and Ryo Yamasaki and Seiji Kikuchi and Jun-Ichi Kira",
year = "2016",
month = "9",
day = "6",
doi = "10.1186/s12974-016-0695-3",
language = "English",
volume = "13",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis

T2 - A cross-sectional study

AU - nakamura, yuri

AU - Matsushita, Takuya

AU - Sato, Shinya

AU - Niino, Masaaki

AU - Fukazawa, Toshiyuki

AU - Yoshimura, Satoshi

AU - Hisahara, Shin

AU - Isobe, Noriko

AU - Shimohama, Shun

AU - watanabe, mitsuru

AU - Yoshida, Kazuto

AU - Houzen, Hideki

AU - Miyazaki, Yusei

AU - Yamasaki, Ryo

AU - Kikuchi, Seiji

AU - Kira, Jun-Ichi

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Background: Higher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS. Methods: We enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity. Results: The HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p corr =0.0004 and p corr =0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p=0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p=0.0012 and p<0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p=0.0415, p=0.0026, and p<0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p=0.0198). Conclusions: Living at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.

AB - Background: Higher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS. Methods: We enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity. Results: The HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p corr =0.0004 and p corr =0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p=0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p=0.0012 and p<0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p=0.0415, p=0.0026, and p<0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p=0.0198). Conclusions: Living at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.

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DO - 10.1186/s12974-016-0695-3

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