Ankylosing spondylitis susceptibility and severity--contribution of TNF gene promoter polymorphisms at positions -238 and -308.
Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position -238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the -308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions -238 and -308 could have a small influence on AS susceptibility and prognosis.
Sousa
Elsa
E
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Caetano-Lopes
Joana
J
Pinto
Patrícia
P
Pimentel
Fernando
F
Teles
José
J
Canhão
Helena
H
Rodrigues
Ana
A
Resende
Catarina
C
Mourão
Ana Filipa
AF
Ribeiro
Célia
C
Pinto
Teresa Laura
TL
Rosa
Carlos Miranda
CM
da Silva
José Alberto Pereira
JA
Branco
Jaime
J
Ventura
Francisco
F
Queiroz
Mário Viana
MV
Fonseca
João Eurico
JE
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha