MEFV E148Q variant is more associated with familial Mediterranean fever when combined with other non-exon 10 MEFV variants in Japanese patients with recurrent fever
MEFV E148Q variant is more associated with familial Mediterranean fever when combined with other non-exon 10 MEFV variants in Japanese patients with recurrent fever
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DOI：
10.1080/14397595.2021.1880534
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发表时间：
2021-01-25
影响因子：
2.2
通讯作者：
Ida, Hiroaki
中科院分区：
文献类型：
--
作者：
Fujimoto, Kyoko;Hidaka, Yukiko;Ida, Hiroaki
目的探讨家族性地中海热（FMF）患者MEFV基因变异p.Glu148Gln （E148Q）的遗传特征，并探讨其在日本复发性发热患者中的意义。方法对211例日本复发性发热患者包括MEFV在内的系统性自身炎症性疾病（SAIDs）的临床表型和基因组变异进行分析。通过下一代外显子测序进行遗传分析，包括外显子-内含子边界。结果12例患者符合非FMF类炎性疾病的诊断标准。199例反复发热患者中，临床诊断为FMF的137例（68.8%）。虽然bonferroni校正p值未达到显著水平，但含有杂合E148Q和其他变异的组发生FMF表型的风险往往高于仅含有杂合E148Q的组（名义p = 0.036）。E148Q等变异杂合组与非E148Q杂合组FMF表型表达比较，差异无统计学意义（标称p = 1.00）。结论E148Q和其他杂合型的患者FMF表型的表达高于E148Q杂合型的患者，提示除E148Q外的其他变异和外显子10变异可能对FMF表型有贡献。
ObjectiveTo investigate the genetic characteristics of one of the MEFV gene variants, p.Glu148Gln (E148Q), in patients with familial Mediterranean fever (FMF) and examine its significance in Japanese patients with recurrent fever.MethodsThe clinical phenotype and genomic variants of systemic autoinflammatory diseases (SAIDs), including MEFV, were analyzed in 211 Japanese patients with recurrent fever. Genetic analysis was performed via next-generation sequencing of exons, including exon-intron boundaries.ResultsTwelve patients met the diagnostic criteria for SAIDs other than FMF. Considering 199 patients with recurrent fever, 137 cases (68.8%) were clinically diagnosed with FMF. Although Bonferroni-adjusted p-value did not reach significance level, the group containing heterozygous E148Q and other variants tended to be at higher risk of developing the FMF phenotype (nominal p = .036) than the group with heterozygous E148Q only. Comparison between the group with heterozygous E148Q and other variants and the heterozygous group containing non-E148Q showed no statistically significant difference in FMF phenotype expression (nominal p = 1.00).ConclusionPatients with heterozygous E148Q and other variants exhibited higher expression of FMF phenotype than those with heterozygous E148Q only, and suggested that other variants than E148Q as well as exon 10 variants might contribute to the FMF phenotype.