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.
| Original language | English |
|---|---|
| Pages (from-to) | 1696-1703 |
| Number of pages | 8 |
| Journal | Multiple Sclerosis Journal |
| Volume | 19 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Nov 2013 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
Cite this
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.
In: Multiple Sclerosis Journal, Vol. 19, No. 13, 11.2013, p. 1696-1703.Research output: Contribution to journal › Article
}
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 - 2013/11
Y1 - 2013/11
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.
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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 -