• Open Access

Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis

Authors

  • Mette Soerensen,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
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  • Mikael Thinggaard,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
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  • Marianne Nygaard,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
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  • Serena Dato,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
    3. Department of Cell Biology, University of Calabria, Ponte Pietro Bucci cubo 4C, 87036 Rende (Cs), Italy
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  • Qihua Tan,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
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  • Jacob Hjelmborg,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
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  • Karen Andersen-Ranberg,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
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  • Tinna Stevnsner,

    1. The Danish Aging Research Center, Department of Molecular Biology, Aarhus University, C. F. Moellers Allé 3, 8000 Aarhus C, Denmark
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  • Vilhelm A. Bohr,

    1. The Danish Aging Research Center, Department of Molecular Biology, Aarhus University, C. F. Moellers Allé 3, 8000 Aarhus C, Denmark
    2. Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, 251 Bayview Blvd., Baltimore, MD, USA
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  • Masayuki Kimura,

    1. The Center for Human Development and Aging, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
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  • Abraham Aviv,

    1. The Center for Human Development and Aging, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
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  • Kaare Christensen,

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
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  • Lene Christiansen

    1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark
    2. Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
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Mette Soerensen, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. Tel.: 0045 65412822; fax: 0045 65414875; e-mail: msoerensen@health.sdu.dk

Summary

Telomerase is of key importance for telomere maintenance, and variants of the genes encoding its major subunits, telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), are candidates for interindividual variation in telomere length. Recently, the two SNPs rs3772190 and rs12696304 in the TERC locus were reported to be associated with leukocyte telomere length (LTL) in two genome-wide association studies, while one haplotype of TERT (rs2853669, rs2736098, rs33954691, and rs2853691) has been reported to be associated with both LTL and longevity in a candidate gene study. In this study, we investigated the two TERC and four TERT SNPs in middle-aged, old, and oldest-old Danes (58–100 years) and their association with LTL (n = 864) and longevity (n = 1069). Furthermore, data on 11 TERT tagging SNPs in 1089 oldest-old and 736 middle-aged Danes were investigated with respect to longevity. For all SNPs, the association with longevity was investigated using both a cross-sectional and a longitudinal approach. Applying an additive model, we found association of LTL with the minor TERC alleles of rs3772190 (A) and rs12696304 (G), such that a shorter LTL was seen in rs3772190 A carriers (regression coefficient = −0.08, P = 0.011) and in male rs12696304 G carriers (regression coefficient = −0.13, P = 0.014). No TERT variations showed association. Moreover, the A allele of rs3772190 (TERC) was found to be associated with longevity [hazard rate (AG + AA) = 1.31, P = 0.006]. No associations with longevity were observed for the TERT SNPs or haplotypes. Our study, thus, indicates that TERC is associated with both LTL and longevity in humans.

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