Predicting genetic risk factors for AA amyloidosis in Algerian patients with familial Mediterranean fever

Premier auteur : Djouher Ait-Idir

Revue :  Molecular Genetics and Genomics

Reference :   https://doi.org/10.1007/s00438-024-02133-6

Lien vers l’article : https://pubmed.ncbi.nlm.nih.gov/38451362/

Introduction:

Amyloid-associated renal amyloidosis (AA) is a severe complication of familial Mediterranean fever (FMF). Its occurrence has been reported to be associated with polymorphisms in the serum amyloid A1 (SAA1) gene and variants in the MEFV gene, associated with FMF respectively.

In Algeria, the association between SAA1 variants and FMF-related amyloidosis had not been studied, hence the aim of this case-control study.

Methods:

120 subjects were included including 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis and 21 without). All were genotyped for SAA1 alleles (SAA1.1, SAA1.5 and SAA1.3), and a subset for the 13 C/T polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were made using the chi-square and Fisher tests.

Results:

Among the 39 FMF patients with AA amyloidosis, there were 18 males for 21 females; mean age was 39.5 years with a mean age at onset of FMF of 11.5 years and a mean number of FMF progression years of 24.5 years; In 36% of cases there was consanguinity and a family history. 77% were treated with colchicine. There was no significant difference for these elements compared with FMF patients without amyloidosis.

The SAA1.1/1.1 genotype was predominant in patients with FMF complicated with AA amyloidosis compared with patients with FMF without amyloidosis (p = 0.001) and controls (p < 0.0001).

The SAA1.1/1.5 genotype was higher in patients without amyloidosis (p = 0.0069) and controls (p = 0.0082) than in patients with amyloidosis.

Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1. 1/1.3 [OR 5.700; 95% CI: 1.435-22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119).

The SAA1.1/1.5 - 13 C/C genotype group [OR 0.152; 95% CI: 0.040-0.587] (p = 0.0062) was protective against amyloidosis.

In all groups, the -13 C/C genotype predominated and was not associated with renal complications [OR 0.88; 95% CI: 0.07-10.43] (p = 0.915).

Discussion and conclusion:

In conclusion, unlike the -13 C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population with familial Mediterranean fever.

National Protocol for Diagnosis and Care of Familial Mediterranean Fever

S. Georgin-Laviallea,h,∗, L. Saveya,h, L. Cuissetc, G. Boursiere,h, J.-J. Boffab,h,

M. Delplanquea,h, R. Bourguibaa,h, J.-B. Monfortd,h, I. Touitoue,h, G. Grateaua,h,

I. Kone-Pautf,h, V. Hentgeng,h, Collaborators1

Summary:

Familial Mediterranean Fever is the world's most common monogenic autoinflammatory disease. It mainly affects people from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood, associated with abdominal and/or thoracic pain lasting an average of 2 to 3 days, and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis of large joints such as the knees and ankles, myalgia of the lower limbs and pseudo-eryzipelas of the ankles. Its most severe complication is inflammatory amyloidosis, or AA amyloidosis, which can lead to renal failure. Treatment is based on colchicine, which helps prevent relapses and the onset of renal amyloidosis.

This work presents national recommendations for the diagnosis, management and follow-up of Familial Mediterranean Fever in France, where we estimate there are between 5,000 and 10,000 patients with the disease at all stages of life. Diagnosis is suspected on the basis of clinical and anamnestic elements, and confirmed by genetic analysis. These recommendations also propose a “treat-to-target” approach to disease treatment, particularly in cases of suspected colchicine resistance - a very rare situation that should remain a situation of elimination, particularly after verification of colchicine compliance. Two special situations are also addressed in these recommendations: renal failure and pregnancy.

​© 2023 Publié par Elsevier Masson SAS au nom de Société Nationale Franc¸ aise de Médecine Interne (SNFMI).

French recommandation for the diagnostic and care of FMF Rev Med int

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