title: Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease?
abstract: Genetic factors associated with rheumatoid arthritis (RA) might involve variant tumour necrosis factor (TNF)-alpha genes. Therefore, polymorphisms at positions -308, -238, -376, -163 and +70 relative to the transcription initiation site were studied with respect to the susceptibility to, or severity of, RA. TNF-alpha genotypes of 283 RA patients and 116 healthy individuals were determined. Clinical data were obtained from patient files and questionnaires. The distribution of TNF-alpha alleles was similar in RA patients and healthy controls. With respect to disease severity, the TNF-alpha -238GA genotype was found to be associated with the absence of erosions [odds ratio (OR) 4.1, confidence interval 1.0-17]. In addition, this genotype was associated with a lower number of hand joints affected by erosions within the first 3 yr of disease onset compared to -238GG. The association between the -238 polymorphism and radiographic progression was independent of the presence of HLA-DR4. In line with this observation, the OR for the presence of erosions in patients with both risk factors (DR4 and -238GG) compared to patients who lack these factors was 11.1 (1.8-6.8). No associations between the TNF-alpha -308, +70 and -376 alleles and susceptibility to, or severity of, RA could be demonstrated. Our data indicate that the TNF-alpha -238GA genotype is associated with decreased radiologically detectable progression of RA.
authors.affiliation: Department of Rheumatology, University Hospital Leiden, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: Brinkman
authors.forename: T W
authors.initials: TW
authors.lastname: Huizinga
authors.forename: S S
authors.initials: SS
authors.lastname: Kurban
authors.forename: E A
authors.initials: EA
authors.lastname: van der Velde
authors.forename: G M
authors.initials: GM
authors.lastname: Schreuder
authors.forename: J M
authors.initials: JM
authors.lastname: Hazes
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000225:Adenine / Q000737:chemistry; D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D003596:Cytosine / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D005838:Genotype; D006147:Guanine / Q000737:chemistry; D015804:HLA-DR4 Antigen / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D017931:DNA Primers; D015804:HLA-DR4 Antigen; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D003596:Cytosine; D000225:Adenine