@article{oai:soar-ir.repo.nii.ac.jp:00020216, author = {Yasunami, Michio and Nakamura, Hitomi and Agematsu, Kazunaga and Nakamura, Akinori and Yazaki, Masahide and Kishida, Dai and Yachie, Akihiro and Toma, Tomoko and Masumoto, Junya and Ida, Hiroaki and Koga, Tomohiro and Kawakami, Atsushi and Eguchi, Katsumi and Furukawa, Hiroshi and Nakamura, Tadashi and Nakamura, Minoru and Migita, Kiyoshi}, issue = {5}, journal = {PLOS ONE}, month = {May}, note = {Objectives
The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes.
Methods
Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment.
Results
The carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni’s correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1*15:02 was completely disappeared in the co-existence of B*40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B*35:01 allele, giving OR of 4.82 (p = 0.0041).
Conclusions
The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations., Article, PLOS ONE.10(5):e0125938(2014)}, title = {Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever}, volume = {10}, year = {2014} }