Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease?

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...

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Published inBritish journal of rheumatology Vol. 36; no. 5; p. 516
Main Authors Brinkman, B M, Huizinga, T W, Kurban, S S, van der Velde, E A, Schreuder, G M, Hazes, J M, Breedveld, F C, Verweij, C L
Format Journal Article
LanguageEnglish
Published England 01.05.1997
Subjects
Adenine - chemistry
Adult
Aged
Alleles
Arthritis, Rheumatoid - genetics
Base Sequence
Case-Control Studies
Cytosine - chemistry
Disease Progression
Disease Susceptibility
DNA Primers - chemistry
Female
Gene Expression Regulation
Gene Frequency
Genes - genetics
Genotype
Guanine - chemistry
HLA-DR4 Antigen - chemistry
HLA-DR4 Antigen - genetics
Humans
Male
Middle Aged
Polymorphism, Genetic
Severity of Illness Index
Surveys and Questionnaires
Tumor Necrosis Factor-alpha - genetics
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Summary: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.
ISSN:0263-7103