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.
BACKGROUND: The G allele of NOTCH4rs422951 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.
Entities:
Keywords:
NOTCH4; Multiple sclerosis; genetics; human leukocyte antigen; polymorphism
Authors: Milena A Gianfrancesco; Pernilla Stridh; Xiaorong Shao; Brooke Rhead; Jennifer S Graves; Tanuja Chitnis; Amy Waldman; Timothy Lotze; Teri Schreiner; Anita Belman; Benjamin Greenberg; Bianca Weinstock-Guttman; Gregory Aaen; Jan M Tillema; Janace Hart; Stacy Caillier; Jayne Ness; Yolanda Harris; Jennifer Rubin; Meghan Candee; Lauren Krupp; Mark Gorman; Leslie Benson; Moses Rodriguez; Soe Mar; Ilana Kahn; John Rose; Shelly Roalstad; T Charles Casper; Ling Shen; Hong Quach; Diana Quach; Jan Hillert; Anna Hedstrom; Tomas Olsson; Ingrid Kockum; Lars Alfredsson; Catherine Schaefer; Lisa F Barcellos; Emmanuelle Waubant Journal: Mult Scler Date: 2017-10-05 Impact factor: 6.312
Authors: Bao Zhang; Qian Rui Fan; Wen Hao Li; Ning Lu; Dong Ke Fu; Yan Jie Kang; Na Wang; Teng Li; Xiao Peng Wen; Da Xu Li Journal: Biomed Res Int Date: 2015-10-28 Impact factor: 3.411