About 200 sequence variations of the Mediterranean fever (MEFV) gene have been described. Even though the role of the three most frequent mutations located in exon 10 of the MEFV gene (M694V, V726A, M680I) in development of FMF has been widely recognized, the role of E148Q which was initially described as disease causing allele is yet controversial. Therefore the aim of this study is to assess the frequency of E148Q among FMF patients and healthy controls (HCs) based on the data from the published case control studies.
We conducted a systematic literature search using PubMed, Embase and The Cochrane Library. Search terms were “MEFV” and “MEFV gene”. Hand searching of the reference lists of key articles and, hand/electronic searching of abstract books of the relevant conferences were performed. Statistical analysis was carried out using the Comprehensive Meta-Analysis statistical software (Biosta, Englewood, NJ, USA). Random-effects model was used .
A total of 536 studies were identified of which 29 were retrieved for full review. Three of them assessed the frequency of MEFV variations in 11 ethnically different populations. A total of 13946 alleles of FMF patients and 9556 of HCs were included in the meta-analysis which yielded an overall odds ratio (OR) of 1.8 (95% CI 1.3–2.6) for E148Q in susceptibility to FMF. As the target populations in these studies show wide variation with regard to FMF prevalence, a subgroup-based meta-analysis was performed which revealed an OR of 1.3 (95% CI 0.9–1.8) and 6.1 (95% CI 3.3–11.3) in populations with high (Jews, Turks, Arabs and Armenians) and low prevalence (Greek, Japanese, Spanish and others), respectively (Figure 1). Homozygosity for E148Q was identified in 15/1875 FMF patients and 8/1878 healthy subjects in 17 studies which appropriate information was provided (p=0.144). On the other hand a clear association of M694V, M680I and V726A with FMF were observed in the pooled analysis.
Our results indicate that the presence of E148Q does not appear to be associated with an increased risk of FMF in populations with high disease prevalence whereas it may be associated with an increased risk in populations with low disease prevalence. However, in these latter populations further research is required to eliminate the role of over-emphasis on genetic testing which may lead to an over diagnosis of FMF.
Disclosure: S. Akar, None; D. Solmaz, None; F. Onen, None; V. Gerdan, None; O. Soysal, None; N. Akkoc, None.