Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis.
OBJECTIVE: The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti-TNF therapy have implicated TNFalpha in the etiopathogenesis of juvenile oligoarthritis. Although the locus is polymorphic, no study has investigate...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1826259925539487744 |
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| author | Zeggini, E Thomson, W Kwiatkowski, D Richardson, A Ollier, W Donn, R |
| author_facet | Zeggini, E Thomson, W Kwiatkowski, D Richardson, A Ollier, W Donn, R |
| author_sort | Zeggini, E |
| collection | OXFORD |
| description | OBJECTIVE: The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti-TNF therapy have implicated TNFalpha in the etiopathogenesis of juvenile oligoarthritis. Although the locus is polymorphic, no study has investigated all TNF single-nucleotide polymorphisms (SNPs) with respect to disease. The aim of this study was to examine the association of multiple TNF SNPs with juvenile oligoarthritis and to construct and analyze SNP-tagged TNF haplotypes. METHODS: A total of 144 simplex families consisting of parent and affected child, as well as 88 healthy, unrelated control subjects were available for study. In these individuals, 9 polymorphic positions of TNF were typed by a high-throughput genotyping method based on the SNaPshot assay. The chi-square and extended transmission disequilibrium tests were used to test for association and linkage, respectively. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were also calculated. Haplotype-tagging SNPs (htSNPs) for the locus were identified by ordering the haplotypes according to their frequencies. RESULTS: The study detected association of several TNF SNPs and established linkage of the locus to juvenile oligoarthritis. The most significant association observed was between the intronic +851 TNF SNP and the persistent oligoarthritis subgroup (OR 3.86, 95% CI 1.6-9.2). Haplotype data mining showed that only 4 of the 9 SNPs need to be typed in order to capture the most frequent TNF haplotypes. CONCLUSION: The TNF locus is linked and associated with juvenile oligoarthritis. Information on the htSNPs can be useful in genetic studies of diseases in which TNF may be of relevance. |
| first_indexed | 2024-03-06T18:57:32Z |
| format | Journal article |
| id | oxford-uuid:125b1937-102f-440d-b1e2-0de87ef1da20 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:57:32Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:125b1937-102f-440d-b1e2-0de87ef1da202022-03-26T10:07:32ZLinkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:125b1937-102f-440d-b1e2-0de87ef1da20EnglishSymplectic Elements at Oxford2002Zeggini, EThomson, WKwiatkowski, DRichardson, AOllier, WDonn, R OBJECTIVE: The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti-TNF therapy have implicated TNFalpha in the etiopathogenesis of juvenile oligoarthritis. Although the locus is polymorphic, no study has investigated all TNF single-nucleotide polymorphisms (SNPs) with respect to disease. The aim of this study was to examine the association of multiple TNF SNPs with juvenile oligoarthritis and to construct and analyze SNP-tagged TNF haplotypes. METHODS: A total of 144 simplex families consisting of parent and affected child, as well as 88 healthy, unrelated control subjects were available for study. In these individuals, 9 polymorphic positions of TNF were typed by a high-throughput genotyping method based on the SNaPshot assay. The chi-square and extended transmission disequilibrium tests were used to test for association and linkage, respectively. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were also calculated. Haplotype-tagging SNPs (htSNPs) for the locus were identified by ordering the haplotypes according to their frequencies. RESULTS: The study detected association of several TNF SNPs and established linkage of the locus to juvenile oligoarthritis. The most significant association observed was between the intronic +851 TNF SNP and the persistent oligoarthritis subgroup (OR 3.86, 95% CI 1.6-9.2). Haplotype data mining showed that only 4 of the 9 SNPs need to be typed in order to capture the most frequent TNF haplotypes. CONCLUSION: The TNF locus is linked and associated with juvenile oligoarthritis. Information on the htSNPs can be useful in genetic studies of diseases in which TNF may be of relevance. |
| spellingShingle | Zeggini, E Thomson, W Kwiatkowski, D Richardson, A Ollier, W Donn, R Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title | Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title_full | Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title_fullStr | Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title_full_unstemmed | Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title_short | Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. |
| title_sort | linkage and association studies of single nucleotide polymorphism tagged tumor necrosis factor haplotypes in juvenile oligoarthritis |
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