Volume 46, Issue 12 pp. 3304-3311

Research Article

Linkage and association studies of single-nucleotide polymorphism–tagged tumor necrosis factor haplotypes in juvenile oligoarthritis

Eleftheria Zeggini,

Corresponding Author

Eleftheria Zeggini

[email protected]

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

Eleftheria Zeggini's work was supported by the Arthritis Research Campaign.

ARC/EU, Stopford Building, Oxford Road, Manchester M13 9PT, UKSearch for more papers by this author

Wendy Thomson,

Wendy Thomson

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

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Dominic Kwiatkowski,

Dominic Kwiatkowski

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

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Anna Richardson,

Anna Richardson

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

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William Ollier,

William Ollier

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

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Rachelle Donn,

Rachelle Donn

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

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The British Paediatric Rheumatology Study Group,

The British Paediatric Rheumatology Study Group

Contributors to The British Paediatric Rheumatology Study Group are as follows: M. Abinun, MD, M. Becker, MD, A. Bell, MD, A. Craft, PhD, E. Crawley, MD, J. David, MD, H. Foster, MD, J. Gardener-Medwin, MD, J. Griffin, MD, A. Hall, MD, M. Hall, MD, A. Herrick, MD, P. Hollingworth, MD, L. Holt, MD, S. Jones, MD, G. Pountain, MD, C. Ryder, MD, T. Southwood, PhD, I. Stewart, MD, P. Woo, PhD, S. Wyatt, MD, H. Venning, MD.

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Eleftheria Zeggini,

Corresponding Author

Eleftheria Zeggini

[email protected]

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

Eleftheria Zeggini's work was supported by the Arthritis Research Campaign.

ARC/EU, Stopford Building, Oxford Road, Manchester M13 9PT, UKSearch for more papers by this author

Wendy Thomson,

Wendy Thomson

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

Search for more papers by this author

Dominic Kwiatkowski,

Dominic Kwiatkowski

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

Search for more papers by this author

Anna Richardson,

Anna Richardson

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

Search for more papers by this author

William Ollier,

William Ollier

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

Search for more papers by this author

Rachelle Donn,

Rachelle Donn

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK

Search for more papers by this author

The British Paediatric Rheumatology Study Group,

The British Paediatric Rheumatology Study Group

Search for more papers by this author

First published: 12 December 2002

https://doi.org/10.1002/art.10698

Citations: 59

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Abstract

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 TNFα 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.

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Citing Literature

Volume46, Issue12

December 2002

Pages 3304-3311

Linkage and association studies of single-nucleotide polymorphism–tagged tumor necrosis factor haplotypes in juvenile oligoarthritis

Abstract

Objective

Methods

Results

Conclusion

REFERENCES

Citing Literature

References

Information

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Linkage and association studies of single-nucleotide polymorphism–tagged tumor necrosis factor haplotypes in juvenile oligoarthritis

Abstract

Objective

Methods

Results

Conclusion

REFERENCES

Citing Literature

References

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