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Distinct genetic profiles between J apanese multiple sclerosis patients with and without B arkhof brain lesions
Author(s) -
Huang Jian,
Isobe Noriko,
Matsushita Takuya,
Yoshimura Satoshi,
Sato Shinya,
Yonekawa Tomomi,
Yamasaki Ryo,
Murai Hiroyuki,
Kira Junichi
Publication year - 2013
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12017
Subject(s) - neuromyelitis optica , multiple sclerosis , genotype , lesion , haplotype , missense mutation , allele , polymerase chain reaction , biology , pathology , medicine , microbiology and biotechnology , mutation , genetics , immunology , gene
Objectives The frequency of brain lesions that fulfil the B arkhof criteria ( B arkhof brain lesions) is low in Asian patients with multiple sclerosis ( MS ). Several genes are associated with MS in the J apanese, but their influence on brain lesion development is unknown. Here, we clarified the genetic profiles of Barkhof brain lesion‐positive and ‐negative MS in the Japanese. Methods We genotyped the HLA ‐ DRB 1 and ‐ DPB 1 alleles, the NOTCH 4 missense mutation rs422951, and the IL ‐7 RA single nucleotide polymorphism rs6897932 in 123 non‐neuromyelitis optica/neuromyelitis optica spectrum disorder MS patients and 367 healthy controls by annealing of sequence‐specific oligonucleotide probes to polymerase chain reaction‐amplified genomic DNA (for the HLA alleles), DNA sequencing (for rs422951), and real‐time polymerase chain reaction using TaqMan genotyping assays (for rs6897932). Results Compared with the healthy controls, the frequency of DRB 1*0405 was significantly higher in the B arkhof brain lesion‐negative group, that of DPB 1*0301 was significantly higher in the B arkhof brain lesion‐positive group, and those of DRB 1*0901 and DPB 1*0401 were significantly lower in the B arkhof brain lesion‐positive group. The frequency of NOTCH 4 rs422951 G allele carriers was significantly lower in both groups compared with the healthy controls, whereas the frequency of the IL ‐7 RA rs6897932 CC genotype was significantly higher in the B arkhof brain lesion‐positive group. Haplotype analyses identified one susceptibility and three resistance haplotypes for B arkhof brain lesion‐positive MS , and two susceptibility and three resistance haplotypes for B arkhof brain lesion‐negative MS . Conclusions The genetic profiles of Japanese MS patients are distinct according to the presence or absence of B arkhof brain lesions.