# The Relationship Between Gene Subtypes, Symptoms, and Cardiac Function in Patients with Familial Mediterranean Fever

## TL;DR

This study shows that different gene subtypes in Familial Mediterranean Fever affect symptoms and heart function differently, highlighting the need for personalized monitoring.

## Contribution

The study identifies distinct clinical and cardiac impacts of specific MEFV gene subtypes in FMF patients.

## Key findings

- Patients with the M694V homozygous mutation had earlier disease onset and worse cardiac function.
- The M694V heterozygous subtype was linked to more frequent arthralgia and better-preserved heart function.
- The M680I heterozygous mutation showed no significant clinical or cardiac associations.

## Abstract

Background/Objectives: Familial Mediterranean fever (FMF) is a chronic autoinflammatory disorder that can affect cardiac structure and function. However, the impact of different Mediterranean fever (MEFV) gene subtypes on clinical features and subclinical cardiac changes remains unclear. This study aimed to evaluate the association between MEFV gene subtypes, clinical features, and cardiac function in patients with FMF. Methods: A total of 98 patients with FMF were prospectively included. Twelve mutations in the MEFV gene were screened, and the M694V homozygous (Gene-1), M694V heterozygous (Gene-2), and M680I heterozygous (Gene-3) subtypes were analyzed. All patients underwent transthoracic echocardiography and speckle-tracking strain analysis. Results: The age of disease onset was earlier in patients carrying the gene-1 mutation compared to mutation-negative patients (11.4 ± 8.0 and 17.6 ± 11.4 years, respectively; p = 0.025). Disease duration was longer in patients with gene-1 mutation (23.3 ± 12.8 and 12.5 ± 9.3 years, respectively; p < 0.001), and disease activity score was higher (6.41 ± 1.9 and 5.15 ± 1.6, respectively; p = 0.007). Furthermore, left atrial contractile strain was significantly lower in this group (−10.6 ± 3.5% and −14.5 ± 6.1%, respectively; p = 0.012). Arthralgia was more frequent in patients with gene-2 mutation (p = 0.026), while left atrial contractile strain was better preserved compared to mutation-negative patients (p = 0.002). No significant association was found between gene-3 mutation and clinical or cardiac parameters. Conclusions: MEFV gene subtypes have different effects on clinical phenotype and cardiac function in FMF. These findings support the importance of genotype-based cardiac monitoring and risk stratification in FMF patients.