title: TMEM187-IRAK1Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin.
abstract: Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containingTMEM187andIRAK1(rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (n= 408) compared with age-matched controls (n= 471) in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts. The rs1059702 C major allele was significantly associated with RA, only with French women. In the French population, the GTC haplotype displayed a protective effect against RA, while the ATC, GCC, and GTT haplotypes conferred significant risk for RA. No association for these haplotypes was found in the Tunisian population. Our results replicated for the first time the association of the three Xq28 polymorphisms with RA risk in Tunisian and French populations and suggested that RA susceptibility is associated withTMEM187-IRAK1polymorphisms in women. Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations.
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France.
authors.forename: Olfa
authors.identifier: 0000-0001-5469-291X
authors.initials: O
authors.lastname: Khalifa
authors.affiliation: Inserm UMRs 1097, Aix-Marseille University, Marseille, France; Rheumatology Department, APHM, Marseille, France.
authors.forename: Nathalie
authors.identifier: 0000-0002-3839-0185
authors.initials: N
authors.lastname: Balandraud
authors.affiliation: Inserm UMRs 1097, Aix-Marseille University, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambert
authors.affiliation: Inserm UMRs 1097, Aix-Marseille University, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Auger
authors.affiliation: Inserm UMRs 1097, Aix-Marseille University, Marseille, France; Rheumatology Department, APHM, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Roudier
authors.affiliation: Inserm, U1051, University Hospital Saint Eloi, Institute for Neurosciences of Montpellier, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sénéchal
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.affiliation: Aix-Marseille University, CNRS, EFS, ADES UMR 7268, 13916 Marseille, France.
authors.forename: Christophe
authors.identifier: 0000-0001-9118-5239
authors.initials: C
authors.lastname: Picard
authors.affiliation: University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Laboratoire d'Immunogénétique Moléculaire, UPR 1142 CNRS, Institute of Human Genetics, Montpellier, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lefranc
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Department of Molecular Genetics, University Hospital of Montpellier, France.
authors.forename: Isabelle
authors.identifier: 0000-0002-5171-1000
authors.initials: I
authors.lastname: Touitou
authors.affiliation: Aix-Marseille University, CNRS, Centrale Marseille, I2M, UMR 7373, 13453 Marseille, France.
authors.forename: Bakridine M'Madi
authors.initials: BM
authors.lastname: Mrenda
authors.affiliation: Aix-Marseille University, CNRS, Centrale Marseille, I2M, UMR 7373, 13453 Marseille, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Benedito
authors.affiliation: Aix-Marseille University, CNRS, Centrale Marseille, I2M, UMR 7373, 13453 Marseille, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Pardoux
authors.affiliation: CNRS UMR 5235, Université de Montpellier, Montpellier, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Gagez
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France.
authors.forename: Yves-Marie
authors.identifier: 0000-0001-5927-3773
authors.initials: YM
authors.lastname: Pers
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.affiliation: Inserm, U 1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France; University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France; Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France.
authors.forename: Florence
authors.identifier: 0000-0003-1762-084X
authors.initials: F
authors.lastname: Apparailly
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005843:Geography; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014416:Tunisia / Q000453:epidemiology
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008565:Membrane Proteins; C000616434:TMEM187 protein, human; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases