TY - JOUR
T1 - Functional variants in the lymphotoxin-α gene predict cardiovascular disease in dialysis patients
AU - Liu, Yongmei
AU - Berthier-Schaad, Yvette
AU - Plantinga, Laura
AU - Fink, Nancy E.
AU - Tracy, Russell P.
AU - Kao, Wen Hong
AU - Klag, Michael J.
AU - Smith, Michael W.
AU - Coresh, Josef
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2006030299
DO - 10.1681/ASN.2006030299
M3 - Article
C2 - 16988060
AN - SCOPUS:33750702840
SN - 1046-6673
VL - 17
SP - 3158
EP - 3166
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -