No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome.
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.
Gottenberg
Jacques-Eric
JE
Rhumatologie, INSERM E 109, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin Bicêtre, France. jegotten@club-internet.fr
Sellam
Jérémie
J
Ittah
Marc
M
Lavie
Frédéric
F
Proust
Alexis
A
Zouali
Habib
H
Sordet
Christelle
C
Sibilia
Jean
J
Kimberly
Robert P
RP
Mariette
Xavier
X
Miceli-Richard
Corinne
C
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*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D003596:Cytosine; D013941:Thymine