title: Telomere-associated polymorphisms correlate with cardiovascular disease mortality in Caucasian women: the Cardiovascular Health Study.
abstract: 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 OBFC1 and TERC, genes related to LTL, was conducted among 3271 Caucasian participants ages ≥65 years enrolled 1989-1990 in the Cardiovascular Health Study. Leukocyte DNA was genotyped for SNPs in OBFC1 (rs4387287 and rs9419958) and TERC (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 OBFC1 SNPs were in linkage disequilibrium (r(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) (P-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) (P-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.
authors.affiliation: Department of Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. aburnett@fhcrc.org
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Burnett-Hartman
authors.forename: Annette L
authors.initials: AL
authors.lastname: Fitzpatrick
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Josh C
authors.initials: JC
authors.lastname: Bis
authors.forename: Russ P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kimura
authors.forename: Abraham
authors.initials: A
authors.lastname: Aviv
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007962:Leukocytes; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics; D012306:Risk; D012737:Sex Factors; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data*
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase