Multiple sclerosis (Houndmills, Basingstoke, England) · 2013
A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese.
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Huang Jian, Yoshimura Satoshi, Isobe Noriko, Matsushita Takuya, Yonekawa Tomomi, Sato Shinya, Yamasaki Ryo, Kira Jun-ichi, South Japan Multiple Sclerosis Genetics Consortium
Аннотация
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, p(corr) =0.0380) while DRB1*0901 was negatively associated (OR=0.32, p(corr) =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.
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, p(corr) =0.0380) while DRB1*0901 was negatively associated (OR=0.32, p(corr) =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.
Предметные рубрики MeSH
AllelesAquaporin 4Confidence IntervalsDNADisease ResistanceFemaleGene FrequencyGenotypeHLA-DRB1 ChainsHaplotypesHumansJapanLinkage DisequilibriumLogistic ModelsMaleMultiple SclerosisMutation, MissenseNeuromyelitis OpticaPolymerase Chain ReactionPolymorphism, Single NucleotideProto-Oncogene ProteinsReceptor, Notch4Receptors, Dopamine D1Receptors, Notch