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BMC Med Genet. 2015 Jul 23;16:52. doi: 10.1186/s12881-015-0194-x.

Sequence variation in telomerase reverse transcriptase (TERT) as a determinant of risk of cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study.

Author information

1
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston, TX, 77030, USA. Jan.Bressler@uth.tmc.edu.
2
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, 135 Dauer Drive, Chapel Hill, NC, 27599, USA. noraf@unc.edu.
3
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, 1300 South Second Street, Minneapolis, MN, 55454, USA. ewd@umn.edu.
4
Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. tmosley@umc.edu.
5
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, 1300 South Second Street, Minneapolis, MN, 55454, USA. folsom@epi.umn.edu.
6
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston, TX, 77030, USA. Eric.Boerwinkle@uth.tmc.edu.
7
Human Genome Sequencing Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA. Eric.Boerwinkle@uth.tmc.edu.

Abstract

BACKGROUND:

Telomerase reverse transcriptase (TERT) maintains telomere ends during DNA replication by catalyzing the addition of short telomere repeats. The expression of telomerase is normally repressed in somatic cells leading to a gradual shortening of telomeres and cellular senescence with aging. Interindividual variation in leukocyte telomere length has been previously associated with susceptibility to cardiovascular disease. The aim of the present study was to determine whether six variants in the TERT gene are associated with risk of incident coronary heart disease, incident ischemic stroke, and mortality in participants in the biracial population-based Atherosclerosis Risk in Communities (ARIC) study, including rs2736100 that was found to influence mean telomere length in a genome-wide analysis.

METHODS:

ARIC is a prospective study of the etiology and natural history of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline in 1987-1989. Haplotype tagging SNPs in TERT were genotyped using a custom array containing nearly 49,000 SNPs in 2,100 genes associated with cardiovascular and metabolic phenotypes. Cox proportional hazards models were used to assess the association between the TERT polymorphisms and incident cardiovascular disease and mortality over a 20-year follow-up period in 8,907 whites and 3,022 African-Americans with no history of disease at the baseline examination, while individuals with prevalent cardiovascular disease were not excluded from the analyses of mortality.

RESULTS:

After adjustment for age and gender, and assuming an additive genetic model, rs2736122 and rs2853668 were nominally associated with incident coronary heart disease (hazards rate ratio = 1.20, p = 0.02, 95 % confidence interval = 1.03- 1.40) and stroke (hazards rate ratio = 1.17, p = 0.05, 95 % confidence interval = 1.00 - 1.38), respectively, in African-Americans. None of the variants was significantly associated with cardiovascular disease in white study participants or with mortality in either racial group.

CONCLUSIONS:

Replication in additional population-based samples combined with genotyping of polymorphisms in other genes involved in maintenance of telomere length may help to determine whether genetic variants associated with telomere homeostasis influence the risk of cardiovascular disease in middle-aged adults.

PMID:
26201603
PMCID:
PMC4557920
DOI:
10.1186/s12881-015-0194-x
[Indexed for MEDLINE]
Free PMC Article

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