Telomere-associated polymorphisms correlate with cardiovascular disease mortality in Caucasian women: The Cardiovascular Health Study

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• 作者：Andrea N. Burnett-Hartman^a ; ^b ; ^{aburnett@fhcrc.org} ; Annette L. Fitzpatrick^b ; Richard A. Kronmal^c ; Bruce M. Psaty^b ; ^d ; ^e ; ^f ; Nancy S. Jenny^g ; Josh C. Bis^b ; ^f ; Russ P. Tracy^h ; Masayuki Kimuraⁱ ; Abraham Avivⁱ
• 关键词：Telomere length ; OBFC1 ; TERC ; Genetic polymorphisms ; Cardiovascular disease mortality
• 刊名：Mechanisms of Ageing and Development
• 出版年：2012
• 期刊代码：193_00476374
• 类别：med
• 出版时间：May, 2012
• 卷：133
• 期：5
• 页码：275-281
• 文件大小：250 K

摘要

Leukocyte telomere length (LTL) is linked to cardiovascular disease (CVD); however, it is unclear if LTL has an etiologic role in CVD. To gain insight into the LTL and CVD relationship, a cohort study of CVD mortality and single nucleotide polymorphisms (SNPs) in m>OBFC1m> and m>TERCm>, genes related to LTL, was conducted among 3271 Caucasian participants ages 鈮?5 years enrolled 1989-1990 in the Cardiovascular Health Study. Leukocyte DNA was genotyped for SNPs in m>OBFC1m> (rs4387287 and rs9419958) and m>TERCm> (rs3772190) that were previously associated with LTL through genome-wide association studies. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95%confidence intervals (CIs). The m>OBFC1m> SNPs were in linkage disequilibrium (m>rm>² = 0.99), and both SNPs were similarly associated with CVD mortality in women. For women, there was a decreased risk of CVD death associated with the minor allele (rs4387287), HR = 0.7; 95%CI: 0.5-0.9 (CC vs. AC) and HR = 0.5; 95%CI: 0.20-1.4 (CC vs. AA) (m>Pm>-trend <0.01). For men there was no association, HR = 1.0; 95%CI: 0.7-1.3 (CC vs. AC) and HR = 1.7; 95%CI: 0.8-3.6 (CC vs. AA) (m>Pm>-trend = 0.64). These findings support the hypothesis that telomere biology and associated genes may play a role in CVD-related death, particularly among women.