Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever.
Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever.
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DOI：
10.1371/journal.pone.0125938
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Migita K
中科院分区：
文献类型：
--
作者：
Yasunami M;Nakamura H;Agematsu K;Nakamura A;Yazaki M;Kishida D;Yachie A;Toma T;Masumoto J;Ida H;Koga T;Kawakami A;Eguchi K;Furukawa H;Nakamura T;Nakamura M;Migita K
家族性地中海热（FMF）患者MEFV基因型与表型的相关性尚不清楚，尤其是第10外显子无典型MEFV突变的患者。在这种情况下，FMF的风险似乎受到其他因素的影响。HLA多态性对FMF风险的贡献作为修饰基因的强候选者进行了检查。对258例符合改良Tel-Hashomer标准的互不相关的日本FMF患者和299例健康对照者进行了HLA-B和-DRB 1基因型测定。通过比值比（OR）评估携带者状态对FMF风险的影响。HLA的影响也进行了评估的临床形式的FMF，FMF与某些MEFV基因型和秋水仙素治疗的反应性的子集。B*39：01的携带者在患者中增加（OR = 3.25，p = 0.0012），而DRB 1 *15：02的携带者减少（OR = 0.45，p = 0.00050），满足Bonferroni的多重统计检验校正（n = 28，p<0.00179）。DRB 1 *15：02的保护作用在B*40：01共存时完全消失。HLA效应在没有典型MEFV变异等位基因M694 I的患者中普遍增强，这与以下观点一致，即突变的较低突变率是由于修饰基因在发病机制中的较大贡献，但有少数例外。此外，42.9%的14例秋水仙素耐药患者和13.5%的156例秋水仙素应答者具有B*35：01等位基因，OR为4.82（p = 0.0041）。HLA-I类和HLA-II类多态性对日本FMF的不同影响被确定，即使在那些具有高突变率MEFV突变的人中也是如此。
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.
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影响因子：
3.7
作者：
Furukawa H;Kawasaki A;Oka S;Ito I;Shimada K;Sugii S;Hashimoto A;Komiya A;Fukui N;Kondo Y;Ito S;Hayashi T;Matsumoto I;Kusaoi M;Amano H;Nagai T;Hirohata S;Setoguchi K;Kono H;Okamoto A;Chiba N;Suematsu E;Katayama M;Migita K;Suda A;Ohno S;Hashimoto H;Takasaki Y;Sumida T;Nagaoka S;Tsuchiya N;Tohma S
通讯作者：
Tohma S
影响因子：
3.7
作者：
Terao C;Ohmura K;Ikari K;Kochi Y;Maruya E;Katayama M;Yurugi K;Shimada K;Murasawa A;Honjo S;Takasugi K;Matsuo K;Tajima K;Suzuki A;Yamamoto K;Momohara S;Yamanaka H;Yamada R;Saji H;Matsuda F;Mimori T
通讯作者：
Mimori T
影响因子：
168.9
作者：
Ben-Chetrit, E;Levy, M
通讯作者：
Levy, M
影响因子：
--
作者：
Livneh, A;Langevitz, P;Pras, M
通讯作者：
Pras, M
影响因子：
5.5
作者：
Kone-Paut, Isabelle;Hentgen, Veronique;Touitou, Isabelle
通讯作者：
Touitou, Isabelle