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Novel polymorphisms and the definition of promoter ‘alleles’ of the tumor necrosis factor and lymphotoxin α loci: inclusion in HLA haplotypes

Genes & Immunity volume 4, pages 547–558 (2003)Cite this article

Abstract

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) influence a variety of cellular responses and play a complex role in the immune response. Several single nucleotide polymorphisms (SNPs) have been reported in these major histocompatibility complex (MHC)-linked loci; however, a comprehensive examination of polymorphisms in the promoter regions of TNF and LTA has not been carried out and was undertaken here. Seven novel SNPs in LTA were identified by sequence analysis of 69 samples. Eight novel TNF alleles and 16 novel LTA alleles were designated. The TNF alleles clustered into two closely related groups, while the LTA alleles clustered into three distinct groups using phylogenetic and percentage difference analyses. A total of 52 unique TNF-LTA-HLA haplotypes are reported. There appear to be some associations between TNF/LTA alleles and HLA haplotypes, but not with specific HLA alleles. The majority of the SNPs appear to be randomly associated within and between the two loci except for the LTA SNPs at −293, +81 and +369. These observations may provide an explanation for the oftentimes contradictory results of studies associating individual cytokine gene SNPs with expression level phenotypes, HLA and disease.

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Acknowledgements

The authors would like to thank Carolyn Katovich Hurley, PhD for all of her support in this research project and William Klitz, PhD at UC Berkeley for his thorough analysis of our data. This study was supported by funding from the Office of Naval Research N00014-00-1-0898 (CK Hurley) to the CW Bill Young Marrow Donor Recruitment and Research Program. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Navy, the Department of Defense or the US government.

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  1. Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, USA

    P E Posch

  2. Department of Oncology, Georgetown University Medical Center, Washington, DC, USA

    I Cruz, D Bradshaw & B A Medhekar

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Posch, P., Cruz, I., Bradshaw, D. et al. Novel polymorphisms and the definition of promoter ‘alleles’ of the tumor necrosis factor and lymphotoxin α loci: inclusion in HLA haplotypes. Genes Immun 4, 547–558 (2003). https://doi.org/10.1038/sj.gene.6364023

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