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Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans

Genes & Immunity volume 5, pages 505–512 (2004)Cite this article

Abstract

The major inflammatory cytokines interleukin(IL)1β, IL6 and tumor necrosis factor α (TNFα) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.

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Acknowledgements

We are grateful to Dr Alec Roy and Dr Mary-Anne Enoch for subsets of their population datasets, and to Longina Akhtar for assistance with cell culture.

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Authors and Affiliations

  1. Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA

    I Belfer, B Buzas, H Hipp, C Evans, I Lorincz & M B Max

  2. Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

    I Belfer, B Buzas, H Hipp, C Evans, I Lorincz & D Goldman

  3. Department of Health and Human Services, Laboratory of Genomic Diversity, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    M Dean

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  1. I Belfer
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  2. B Buzas
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Correspondence to I Belfer.

Additional information

This study was supported by NIH Intramural Grants Z01 DE00366 and Z01 AA000301, and the Comprehensive Neuroscience Program Grant USUHS G192BR-C4 (Henry Jackson Foundation).

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Belfer, I., Buzas, B., Hipp, H. et al. Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans. Genes Immun 5, 505–512 (2004). https://doi.org/10.1038/sj.gene.6364118

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