title: Characterization of copy number variants for CCL3L1 gene in rheumatoid arthritis for French trio families and Tunisian cases and controls.
abstract: Analyses of copy number variants (CNVs) for candidate genes in complex diseases are currently a promising research field. CNVs of C-C chemokine ligand 3-like 1 (CCL3L1) gene are candidate genomic factors in rheumatoid arthritis (RA). We investigated CCL3L1 CNVs association with a case-control study in Tunisians and a transmission analysis in French trio families. Relative copy number (rCN) of CCL3L1 gene was quantified by droplet digital PCR (ddPCR) in 100 French trio families (RA patients and their two parents) and in 166 RA cases and 102 healthy controls from Tunisia. We calculated odds ratio (OR) to investigate association risk for CCL3L1 CNVs in RA. rCN identified varied from 0 to 4 in the French population and from 0 to 7 in the Tunisian population. A significant difference was observed in the distribution of these rCNs between the two populations (p = 2.34 × 10(-10)), as when rCN from French and Tunisian RA patients were compared (p = 2.83 × 10(-5)). CNVs transmission in French RA trios allowed the characterization of genotypes with the presence of tandem duplication and triplication on the same chromosome. RA association tests highlighted a protective effect of rCN = 5 for CCL3L1 gene in the Tunisian population (OR = 0.056; CI 95 % [0.01-0.46]). Characterization of CCL3L1 CNVs with ddPCR methodology highlighted specific CN genotypes in a French family sample. A copy number polymorphism of a RA candidate gene was quantified, and its significant association with RA was revealed in a Tunisian sample.
authors.affiliation: GenHotel-EA3886, Evry University, 2 rue Gaston Cremieux, 91057, Evry-cedex, France.
authors.forename: Mohamed Sahbi
authors.initials: MS
authors.lastname: Ben Kilani
authors.affiliation: Laboratory of Human Molecular Genetics, Sfax's Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisie.
authors.forename: Yosser
authors.initials: Y
authors.lastname: Achour
authors.affiliation: GenHotel-EA3886, Evry University, 2 rue Gaston Cremieux, 91057, Evry-cedex, France.
authors.forename: Javier
authors.initials: J
authors.lastname: Perea
authors.affiliation: Genetic Department, CHU Clermont Ferrand, GenHotel-Auvergne, EA4679, Auvergne University, 63000, Clermont Ferrand, France.
authors.forename: François
authors.initials: F
authors.lastname: Cornelis
authors.affiliation: Rheumatology Federation, Lariboisiere Hospital, AP-HP, 75010, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.affiliation: GenHotel-EA3886, Evry University, 2 rue Gaston Cremieux, 91057, Evry-cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Chaudru
authors.affiliation: Laboratory of Human Molecular Genetics, Sfax's Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisie.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Maalej
authors.affiliation: GenHotel-EA3886, Evry University, 2 rue Gaston Cremieux, 91057, Evry-cedex, France. elisabeth.teixeira@univ-evry.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000235:genetics*; D056915:DNA Copy Number Variations; D005190:Family; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D014416:Tunisia
chemical_list: C492767:CCL3L1 protein, human; D019742:Chemokines, CC
keywords: CCL3L1 gene; Copy number variants; Genetics; Rheumatoid arthritis