Objectives The frequency of brain lesions that fulfil the Barkhof criteria (Barkhof brain lesions) is low in Asian patients with multiple sclerosis (MS). Several genes are associated with MS in the Japanese, 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-DRB1 and -DPB1 alleles, the NOTCH4 missense mutation rs422951, and the IL-7RA 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 DRB1*0405 was significantly higher in the Barkhof brain lesion-negative group, that of DPB1*0301 was significantly higher in the Barkhof brain lesion-positive group, and those of DRB1*0901 and DPB1*0401 were significantly lower in the Barkhof brain lesion-positive group. The frequency of NOTCH4 rs422951 G allele carriers was significantly lower in both groups compared with the healthy controls, whereas the frequency of the IL-7RA rs6897932 CC genotype was significantly higher in the Barkhof brain lesion-positive group. Haplotype analyses identified one susceptibility and three resistance haplotypes for Barkhof brain lesion-positive MS, and two susceptibility and three resistance haplotypes for Barkhof brain lesion-negative MS. Conclusions The genetic profiles of Japanese MS patients are distinct according to the presence or absence of Barkhof brain lesions.
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