Department of Internal Medicine F and the national FMF center, Sheba Medical Center, Ramat-Gan, 52621 Israel.
Gene. 2012 Jan 10;491(2):260-3. doi: 10.1016/j.gene.2011.10.005. Epub 2011 Oct 13.
Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF gene MEFV (MEditerranean FeVer). It has a large phenotypic diversity even in patients with similar genotypes. Despite evidence that environmental factors (EFs) and genetic factors, including MEFV mutations (such as M694V, E148Q) and background modifier genes (MGs), affect the clinical manifestations of FMF, the relative contribution of each remains unknown.
To investigate the relative contribution of environmental and genetic factors to the phenotype of FMF, we compared the intra-pair clinical concordance of 10 mono and 7 dizygotic twins with FMF. The part played by EFs was determined by the phenotypic discordance of the monozygous twins, and the MGs effect was determined by deducing the environmental effect, computed for MZ twins, from the phenotypic discordance of the dizygous twins.
The mean±SD of intra-pair concordance was higher in the MZ than in DZ twin group (88.1±13.2 vs. 70.7±14.1 respectively, P value<0.05). Based on the concordance in clinical manifestations in MZ and DZ twins, the environmental effect on the phenotype of FMF is estimated as 11.9%±6.6% and the MGs effect as 17.4%±15.5% in average.
In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively.
家族性地中海热（FMF）是一种常染色体隐性疾病，由 MEFV（地中海热）基因中的突变引起。即使在具有相似基因型的患者中，也存在很大的表型多样性。尽管有证据表明环境因素（EFs）和遗传因素，包括 MEFV 突变（如 M694V、E148Q）和背景修饰基因（MGs），会影响 FMF 的临床表现，但每种因素的相对贡献仍不清楚。
为了研究环境和遗传因素对 FMF 表型的相对贡献，我们比较了 10 对单卵双胞胎和 7 对双卵双胞胎的临床同卵性。通过同卵双胞胎的表型不一致性来确定 EF 的作用，通过从双卵双胞胎的表型不一致性中推断出 MZ 双胞胎的环境效应来确定 MGs 的效应。
MZ 双胞胎组的同卵性平均±SD 高于 DZ 双胞胎组（分别为 88.1±13.2 与 70.7±14.1，P 值<0.05）。根据 MZ 和 DZ 双胞胎在临床表现上的一致性，估计 FMF 表型的环境效应为 11.9%±6.6%，MGs 效应为 17.4%±15.5%。
在 FMF 中，表型受 MEFV 突变、MGs 和 EFs 的影响，其比例约为 6:1.5:1。
