Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever.
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4431852?pdf=render |
| _version_ | 1818268268788449280 |
|---|---|
| author | Michio Yasunami Hitomi Nakamura Kazunaga Agematsu Akinori Nakamura Masahide Yazaki Dai Kishida Akihiro Yachie Tomoko Toma Junya Masumoto Hiroaki Ida Tomohiro Koga Atsushi Kawakami Katsumi Eguchi Hiroshi Furukawa Tadashi Nakamura Minoru Nakamura Kiyoshi Migita |
| author_facet | Michio Yasunami Hitomi Nakamura Kazunaga Agematsu Akinori Nakamura Masahide Yazaki Dai Kishida Akihiro Yachie Tomoko Toma Junya Masumoto Hiroaki Ida Tomohiro Koga Atsushi Kawakami Katsumi Eguchi Hiroshi Furukawa Tadashi Nakamura Minoru Nakamura Kiyoshi Migita |
| author_sort | Michio Yasunami |
| collection | DOAJ |
| description | 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.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.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).The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations. |
| first_indexed | 2024-12-12T20:35:48Z |
| format | Article |
| id | doaj.art-de0d799e4e454d619585b7d6f2f4df90 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T20:35:48Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-de0d799e4e454d619585b7d6f2f4df902022-12-22T00:12:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012593810.1371/journal.pone.0125938Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever.Michio YasunamiHitomi NakamuraKazunaga AgematsuAkinori NakamuraMasahide YazakiDai KishidaAkihiro YachieTomoko TomaJunya MasumotoHiroaki IdaTomohiro KogaAtsushi KawakamiKatsumi EguchiHiroshi FurukawaTadashi NakamuraMinoru NakamuraKiyoshi MigitaThe 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.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.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).The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations.http://europepmc.org/articles/PMC4431852?pdf=render |
| spellingShingle | Michio Yasunami Hitomi Nakamura Kazunaga Agematsu Akinori Nakamura Masahide Yazaki Dai Kishida Akihiro Yachie Tomoko Toma Junya Masumoto Hiroaki Ida Tomohiro Koga Atsushi Kawakami Katsumi Eguchi Hiroshi Furukawa Tadashi Nakamura Minoru Nakamura Kiyoshi Migita Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. PLoS ONE |
| title | Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. |
| title_full | Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. |
| title_fullStr | Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. |
| title_full_unstemmed | Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. |
| title_short | Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. |
| title_sort | identification of disease promoting hla class i and protective class ii modifiers in japanese patients with familial mediterranean fever |
| url | http://europepmc.org/articles/PMC4431852?pdf=render |
| work_keys_str_mv | AT michioyasunami identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT hitominakamura identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT kazunagaagematsu identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT akinorinakamura identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT masahideyazaki identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT daikishida identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT akihiroyachie identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT tomokotoma identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT junyamasumoto identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT hiroakiida identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT tomohirokoga identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT atsushikawakami identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT katsumieguchi identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT hiroshifurukawa identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT tadashinakamura identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT minorunakamura identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever AT kiyoshimigita identificationofdiseasepromotinghlaclassiandprotectiveclassiimodifiersinjapanesepatientswithfamilialmediterraneanfever |