title: No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome.
abstract: Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sjögren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals. The only single nucleotide polymorphism frequently observed, namely -871 T/C in the promoter region, was then genotyped in 162 French patients with pSS and 90 French control individuals. No significant differences in allele (T allele frequency: 49.7% in patients with pSS versus 50% in controls; P = 0.94) and genotype frequencies of BAFF polymorphism were detected between pSS patients and control individuals. BAFF gene polymorphism was not associated with a specific pattern of antibody secretion either. T allele carriers had significantly increased BAFF protein serum levels (mean values of 8.6 and 5.7 ng/ml in patients with TT and TC genotypes, respectively, versus 3.3 ng/ml in patients with CC genotype; P = 0.01), although no correlation was observed between BAFF polymorphism and mRNA level. In conclusion, BAFF gene polymorphism is neither involved in genetic predisposition to pSS nor associated with a specific pattern of antibody production.
authors.affiliation: Rhumatologie, INSERM E 109, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin Bicêtre, France. jegotten@club-internet.fr
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.forename: Marc
authors.initials: M
authors.lastname: Ittah
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lavie
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Habib
authors.initials: H
authors.lastname: Zouali
authors.forename: Christelle
authors.initials: C
authors.lastname: Sordet
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
mesh_terms: D000368:Aged; D053264:B-Cell Activating Factor; D016022:Case-Control Studies; D003596:Cytosine; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood; D012859:Sjogren's Syndrome / Q000235:genetics*; D013941:Thymine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D003596:Cytosine; D013941:Thymine