Background: Familial Mediterranean Fever (FMF) is linked with the MEFV gene and is the most common among monogenic autoinflammatory diseases, with high prevalence in the Mediterranean basin. Genetic spectrum significantly impacts clinical presentation and varies between demographically isolated and cosmopolitan populations.

Objectives: To compare the clinical manifestation and genetic profile among 1286 FMF patients from two well-characterized FMF cohorts living in Italy (Apulia) and Türkiye (Istanbul).

Methods: One hundred sixty-five Italian patients (age 38.5±1.6 years, females 54.5%) and 1121 Turkish patients (age 40.4±0.3 years, females 62.5%) followed at referral centers (University of Bari “Aldo Moro” Department of Internal Medicine and Cerrahpasa Medical Faculty, Division of Rheumatology) were interviewed for demographic, clinical, and genetic features. Continuous data were expressed as mean ± standard error of the mean, and categorical data as numbers and percentages.

Results: The study included 165 patients from Italy (mean age 38.5±1.6 years) and 1121 patients from Türkiye (40.4±0.3 years; p=0.3). Females accounted for 54.5% of Italian patients and 62.5% of Turkish patients (p=0.031). The age at FMF diagnosis was comparable between cohorts (29.4±1.6 years in Italians and 25.0±0.4 years in Turkish patients, p=0.05), with a diagnostic delay of more than 5 years in 39.4% of Italians and 46.2% of Turkish patients (p=0.1). Concomitant rheumatic diseases were more frequent in Turkish patients (12.8% vs. 0.6%; p<0.001), as was the rate of appendectomy regarding misdiagnosis (18.8% vs. 7.9%, p<0.001). Italian patients had a higher prevalence of fever (91.5% vs. 83.7%; p=0.009), and a lower prevalence of abdominal pain (60.0% vs. 91.3%, p<0.001) and thoracic pain (20.6% vs. 35.4% p<0.001) compared to Turkish patients. The mean annual frequency of attacks without treatment was lower in Italian than in Turkish patients (12.4±0.8 vs. 19.9±0.6; p<0.001). The mean daily dose of colchicine was significantly higher in Turkish patients compared to the Italian cohort (0.45±0.04 vs. 1.25±0.01, p<0.001). The use of anti-IL-1 agents was more prevalent in the Turkish cohort (7.0%) compared to Italian patients (3.2%, p<0.001). Regarding genetic findings, E148Q/R761H mutations were identified in 41 patients (26.1%) of the Italian cohort, whereas no such mutations were observed in the Turkish cohort (p<0.001). In contrast, the homozygous M694V mutation was absent in the Italian cohort and significantly prevalent among Turkish patients (18.8%, p<0.001). The compound heterozygous M680I/M694V mutation was detected in 77 Turkish patients (7.0%), whereas only one Italian patient (0.6%) exhibited this mutation (p=0.002). The R202Q mutation was found to be significantly more common in the Italian cohort, affecting 30 individuals (19.1%) compared to 52 Turkish patients (4.7%, p<0.001). Overall, homozygous mutations were less prevalent in the Italian cohort (7.6%), compared to 27.5% in Turkish patients (p<0.001). Conversely, heterozygous mutations were more common in Italian patients than in Turkish patients (43.9% vs. 28.0%, p<0.001). Details of the genetic comparison are presented in Table 1.

Conclusion: The more severe disease course observed in the Turkish patients’ cohort could be influenced by demographical differences, whereas the higher prevalence of rare mutations in the Italian cohort underscores the impact of genetic homogeneity of a relatively isolated population. These findings highlight the importance of sociocultural and historical factors in shaping FMF genotypes and their influence on clinical presentation and disease progression.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.