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

Yongmei Liu, Yvette Berthier-Schaad, Laura Plantinga, Nancy E. Fink, Russell P. Tracy, Wen Hong Kao, Michael J. Klag, Michael W. Smith, Josef Coresh

Research output: Contribution to journalArticlepeer-review

Abstract

TNF-β that is encoded by lymphotoxin-α 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.

Original languageEnglish (US)
Pages (from-to)3158-3166
Number of pages9
JournalJournal of the American Society of Nephrology
Volume17
Issue number11
DOIs
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Nephrology

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