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Functional variants in the lymphotoxin-alpha gene predict cardiovascular disease in dialysis patients

  1. Author:
    Liu, Y. M.
    Berthier-Schaad, Y.
    Plantinga, L.
    Fink, N. E.
    Tracy, R. P.
    Kao, W. H.
    Klag, M. J.
    Smith, M. W.
    Coresh, J.

  2. Author Address

    Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NCI, Lab Genomic Divers, SAIC Frederick, Frederick, MD USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD USA. Univ Vermont, Burlington, VT USA.;Coresh, J, Johns Hopkins Univ, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA.;coresh@jhu.edu
    1. Year: 2006
    2. Date: Nov
  2. Journal: Journal of the American Society of Nephrology
    1. 17
    2. 11
    3. Pages: 3158-3166
  4. Type of Article: Article
  5. ISSN: 1046-6673
  1. Abstract:

    TNF-beta that is encoded by lymphotoxin-alpha gene (LTA) regulates adhesion molecules and IL-6. Previously, a genome-wide case-control study showed that LTA gene variants predisposed to cardiovascular disease (CVD). In a prospective study of 775 dialysis patients, LTA and IL-6 gene variants were tested as independent predictors of CVD risk. Four polymorphisms in the LTA gene and one in the IL-6 gene were genotyped. CVD events were ascertained from medical records. During a mean follow-up of 2.6 yr, 294 first-incident CVD events occurred. The LTA 26Asn variant predicted higher adjusted CVD risk (hazard ratio HR 1.33 for each additional copy of Asn allele; 95% confidence interval 1.14 to 1.55; P = 0.0003). Two other nonsynonymous polymorphisms in the LTA, 13Agr and 51Pro, were associated with lower inflammatory activity and CVD risk. LTA haplotypes (based on all four single-nucleotide polymorphisms) were associated with inflammatory markers and predicted CVD risk (P = 0.005) after adjustment. These LTA genotype associations were independent of the IL-6 -174G/C genotype association that was reported recently. LTA and IL-6 gene variants independently predicted risk for CVD among dialysis patients, suggesting that susceptibility in multiple inflammatory pathways contribute to the development of CVD.

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External Sources

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  2. DOI: 10.1681/asn.2006030299
  3. View record in Web of Science®
  4. WOS: 000241912100028

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