A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese

Jian Huang, Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Tomomi Yonekawa, Shinya Sato, Ryo Yamasaki, Jun-Ichi Kira

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20-0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.

元の言語英語
ページ(範囲)1696-1703
ページ数8
ジャーナルMultiple Sclerosis Journal
19
発行部数13
DOI
出版物ステータス出版済み - 1 1 2013

Fingerprint

Neuromyelitis Optica
Missense Mutation
Multiple Sclerosis
Alleles
Odds Ratio
Haplotypes
HLA-DRB1 Chains
Demyelinating Diseases
DNA Sequence Analysis
Gene Frequency
Logistic Models
Genotype
Regression Analysis
Confidence Intervals
HLA-DRB1*04:05 antigen

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

これを引用

A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese. / Huang, Jian; Yoshimura, Satoshi; Isobe, Noriko; Matsushita, Takuya; Yonekawa, Tomomi; Sato, Shinya; Yamasaki, Ryo; Kira, Jun-Ichi.

:: Multiple Sclerosis Journal, 巻 19, 番号 13, 01.01.2013, p. 1696-1703.

研究成果: ジャーナルへの寄稿記事

Huang, Jian ; Yoshimura, Satoshi ; Isobe, Noriko ; Matsushita, Takuya ; Yonekawa, Tomomi ; Sato, Shinya ; Yamasaki, Ryo ; Kira, Jun-Ichi. / A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese. :: Multiple Sclerosis Journal. 2013 ; 巻 19, 番号 13. pp. 1696-1703.
@article{22c7a8c1a4b64c5b90765ec3998e39e6,
title = "A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese",
abstract = "Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9{\%} vs 21.7{\%}, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95{\%} confidence interval (CI)= 0.20-0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.",
author = "Jian Huang and Satoshi Yoshimura and Noriko Isobe and Takuya Matsushita and Tomomi Yonekawa and Shinya Sato and Ryo Yamasaki and Jun-Ichi Kira",
year = "2013",
month = "1",
day = "1",
doi = "10.1177/1352458513482512",
language = "English",
volume = "19",
pages = "1696--1703",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "13",

}

TY - JOUR

T1 - A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese

AU - Huang, Jian

AU - Yoshimura, Satoshi

AU - Isobe, Noriko

AU - Matsushita, Takuya

AU - Yonekawa, Tomomi

AU - Sato, Shinya

AU - Yamasaki, Ryo

AU - Kira, Jun-Ichi

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20-0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.

AB - Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20-0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.

UR - http://www.scopus.com/inward/record.url?scp=84883354784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883354784&partnerID=8YFLogxK

U2 - 10.1177/1352458513482512

DO - 10.1177/1352458513482512

M3 - Article

C2 - 23549433

AN - SCOPUS:84883354784

VL - 19

SP - 1696

EP - 1703

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 13

ER -