title: Polymorphisms of tumor necrosis factor-α promoter region for susceptibility to HLA-B27-positive ankylosing spondylitis in Korean population.
abstract: This study designed to assess the relationship between tumor necrosis factor (TNF)-α promoter polymorphisms and disease susceptibility to human leukocyte antigen (HLA)-B27-positive ankylosing spondylitis (AS). One hundred and nineteen HLA-B27(+) AS patients, 95 HLA-B27(+) healthy controls, and 135 random healthy controls were enrolled in this study. Six single nucleotide polymorphisms (SNPs) of the TNF-α promoter at positions -1031T/C, -863C/A, -857C/T, -646G/A, -308G/A, and -238G/A were analyzed. Differences between groups were evaluated using the chi-square test or Fisher's exact test. Haplotypes from each SNP were constructed, and differences in haplotypic frequencies between groups were evaluated. There were significant differences in the allelic and genotypic frequencies of 1031T/C, -863C/A, and -857C/T TNF-α promoters polymorphisms between HLA-B27(+) AS patients and random controls, but not between patients with AS and HLA-B27(+) healthy individuals. TNF-α polymorphisms did not influence the extra-spinal clinical features in patients with AS. The haplotypic sequence -1031T/-863C/-857C/-308G increased the risk of susceptibility to AS compared to random controls (P (corr) < 0.001, OR = 2.756, 95% CI = 1.894-4.010), whereas the sequence -1031C/-863A/-857C/-308G appeared to be associated with decreased susceptibility to AS compared to random controls (P (corr) = 0.006, OR = 0.396, 95% CI = 0.231-0.679). This study indicates that TNF-α promoter polymorphism between controls and AS patients with HLA-B27(+) genetic background is not associated with susceptibility to AS. However, TNF-α polymorphism, irrespective of HLA-B27, increases risk of susceptibility to AS in general population.
authors.affiliation: Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea.
authors.forename: Won-Tae
authors.initials: WT
authors.lastname: Chung
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.forename: Won Cheoul
authors.initials: WC
authors.lastname: Jang
authors.forename: Su Min
authors.initials: SM
authors.lastname: Park
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Ahn
authors.forename: Il Kyu
authors.initials: IK
authors.lastname: Yoon
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Youn-Hyoung
authors.initials: YH
authors.lastname: Nam
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha