The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF).
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively.
Department of Internal Medicine F and the national FMF center, Sheba Medical Center, Ramat-Gan, 52621 Israel. Ilan.Benzvi@sheba.health.gov.il
Ilan
I
Ben-Zvi
Benny
B
Brandt
Yackov
Y
Berkun
Merav
M
Lidar
Avi
A
Livneh
D000293:Adolescent; D000328:Adult; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004777:Environment; D010505:Familial Mediterranean Fever / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D000071198:Pyrin
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin