title: The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever.
abstract: Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end-stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end-stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients.
authors.affiliation: Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene, Alger, Algeria; Faculté des Sciences, Université M'Hamed Bougara de Boumerdès, Avenue de l'indépendance, 35000 Boumerdès, Algeria. Electronic address: aitidir.djouher@gmail.com.
authors.forename: Djouher
authors.initials: D
authors.lastname: Ait-Idir
authors.affiliation: Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene, Alger, Algeria.
authors.forename: Bahia
authors.initials: B
authors.lastname: Djerdjouri
authors.affiliation: Faculté des Sciences, Université M'Hamed Bougara de Boumerdès, Avenue de l'indépendance, 35000 Boumerdès, Algeria.
authors.forename: Faiza
authors.initials: F
authors.lastname: Bouldjennet
authors.affiliation: Qatar Biomedical Research Institute, Doha, Qatar.
authors.forename: Rowaida Z
authors.initials: RZ
authors.lastname: Taha
authors.affiliation: Qatar Biomedical Research Institute, Doha, Qatar; School of Medicine, University of Jordan, Amman, Jordan; University of Iowa College of Medicine, Iowa City, IA, USA.
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
authors.affiliation: Service de Néphrologie-Hémodialyse, Centre Hospitalo-Universitaire, Tlemcen, Algeria.
authors.forename: Rawda
authors.initials: R
authors.lastname: Sari-Hamidou
authors.affiliation: Service de Néphrologie Dialyses et Transplantation Rénale, Centre Hospitalo-Universitaire, Beni-Messous, Alger, Algeria.
authors.forename: Ghalia
authors.initials: G
authors.lastname: Khellaf
authors.affiliation: Service de Néphrologie-Hémodialyse, Centre Hospitalo-Universitaire, Tlemcen, Algeria.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Benmansour
authors.affiliation: Service de Néphrologie Dialyses et Transplantation Rénale, Centre Hospitalo-Universitaire, Beni-Messous, Alger, Algeria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benabadji
authors.affiliation: Service de Néphrologie-Transplantation, Centre Hospitalo-Universitaire Mustapha, Algeria.
authors.forename: Farid
authors.initials: F
authors.lastname: Haddoum
mesh_terms: D000293:Adolescent; D000328:Adult; D000462:Algeria; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002648:Child; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000071198:Pyrin / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin
keywords: Algeria; Familial Mediterranean fever; MEFV gene; Renal AA-amyloidosis; p.M694I