Authors observed that R202Q is found frequently among non-carrier chromosomes in the families as well as in unrelated controls: 20% of chromosomes from unrelated controls (CEPH panel, at least 120 chromosomes), in 9/56 non-carrier chromosomes in the FMF families and 19/123 carrier chromosomes. Thus, they conclude this is a common polymorphism. Assuming hardy-weinberg equilibrium, this would be case+: 1, case-: 60, control+: 3, control-: 86.
Four of 26 individuals with Familial Mediterranean Fever were homozygous for this variant, while none of 60 controls were (p-value 0.007). (1) 3yo Armenian female, (2) 4yo Greek female, (3) 12yo Greek female, (4) 14yo Greek male. It was also found as part of a compound heterozygote in (1)12yo Greek female (with M690I and E167D) and (2) a 12yo Greek male (with M694V). The allelic frequency in N. Greece is 0.125. Previous reports have declared this a polymorphism, but the lack of other mutations in the homozygous cases and the favorable response to colchicine cause the authors to consider this pathogenic.
This variant was seen homozygously in 14/152 individuals with FMF (12 of whom harbored no additional disease-associated mutation in MEFV), and was seen homozygously in 1/140 healthy controls. The typical symptoms were fever, serositis and monoarthritis in contrast to abdominal pain. Colchicine was reported as causing significant clinical improvement.
In a study of SNPs related to ulcerative colitis, this variant was found with an allelic frequency of 0.27 in 591 controls and 0.26 in 228 cases. If these variants are assumed to be in Hardy-Weinberg Equilibrium and these individuals are assumed to not have Familial Mediterranean Fever, this would be 79/646 controls.