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IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study

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Abstract

Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05–1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.

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Acknowledgments

This study was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01 HC-15103, and grant R01 HL-071862-03 (Dr Reiner) from the National Heart, Lung, and Blood Institute, and by the National Institute on Aging, Claude D. Pepper Older Americans Independence Centers, Grant P30 AG021334, and RO1 AGO27236 (Dr. Walston). The funding organization participated in the design and conduct of CHS and monitored the study’s data collection efforts and management. The funding organization did not participate in analysis and interpretation of the data for the manuscript but reviewed it for accuracy of the CHS study description and acknowledgment of study investigators and funding sources. A full list of participating CHS investigators and institutions can be found at http://www.chs-nhlbi.org. We thank Jill Perrotte B. S., and Kate M. Durda, Department of Pathology, University of Vermont College of Medicine, Burlington, for assistance with genotyping and Jia Y. Wan for assistance with data analysis. All received support from the National Heart, Lung, and Blood Institute grant R01 HL-071862-03 for their contribution.

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Authors and Affiliations

  1. Johns Hopkins Medical Institutions, Johns Hopkins University, John R Burton Pavilion, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224, USA

    Jeremy D. Walston & M. Daniele Fallin

  2. University of Washington, Seattle, WA, USA

    Bruce Psaty & Alex Reiner

  3. University of Vermont, Colchester, VT, USA

    Mary Cushman, Nancy Jenny, Russell Tracy & Peter Durda

  4. California Pacific Medical Center, San Francisco, CA, USA

    Warren Browner

  5. University of North Carolina, Chapel Hill, NC, USA

    Leslie Lange

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  1. Jeremy D. Walston
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Correspondence to Jeremy D. Walston.

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Walston, J.D., Fallin, M.D., Cushman, M. et al. IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study. Hum Genet 122, 485–494 (2007). https://doi.org/10.1007/s00439-007-0428-x

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  • DOI: https://doi.org/10.1007/s00439-007-0428-x

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