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

Mette Sørensen; Mikael Thinggaard; Marianne Nygaard; Serena Dato; Qihua Tan; Jacob Hjelmborg; Karen Andersen-Ranberg; Tinna V. Stevnsner; Vilhelm Bohr; Masayuki Kimura; Abraham Aviv; Kaare Christensen; Lene Christiansen

doi:10.1111/j.1474-9726.2011.00775.x

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

Mette Sørensen, Mikael Thinggaard, Marianne Nygaard, Serena Dato, Qihua Tan, Jacob Hjelmborg, Karen Andersen-Ranberg, Tinna V. Stevnsner, Vilhelm Bohr, Masayuki Kimura, Abraham Aviv, Kaare Christensen, Lene Christiansen

Institut for Molekylærbiologi og Genetik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

99 Citationer (Scopus)

Abstract

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

Originalsprog	Engelsk
Tidsskrift	Aging Cell
Vol/bind	11
Nummer	2
ISSN	1474-9718
DOI	https://doi.org/10.1111/j.1474-9726.2011.00775.x
Status	Udgivet - apr. 2012

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10.1111/j.1474-9726.2011.00775.x

Citationsformater

Sørensen, M., Thinggaard, M., Nygaard, M., Dato, S., Tan, Q., Hjelmborg, J., Andersen-Ranberg, K., Stevnsner, T. V., Bohr, V., Kimura, M., Aviv, A., Christensen, K., & Christiansen, L. (2012). Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis. Aging Cell, 11(2). https://doi.org/10.1111/j.1474-9726.2011.00775.x

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

abstract = "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",

keywords = "association study, cross-sectional data and longitudinal data, human longevity, leukocyte telomere length, telomerase reverse transcriptase, telomerase RNA component",

author = "Mette S{\o}rensen and Mikael Thinggaard and Marianne Nygaard and Serena Dato and Qihua Tan and Jacob Hjelmborg and Karen Andersen-Ranberg and Stevnsner, {Tinna V.} and Vilhelm Bohr and Masayuki Kimura and Abraham Aviv and Kaare Christensen and Lene Christiansen",

year = "2012",

month = apr,

doi = "10.1111/j.1474-9726.2011.00775.x",

language = "English",

volume = "11",

journal = "Aging Cell",

issn = "1474-9718",

publisher = "Wiley-Blackwell Publishing Ltd",

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Sørensen, M, Thinggaard, M, Nygaard, M, Dato, S, Tan, Q, Hjelmborg, J, Andersen-Ranberg, K, Stevnsner, TV, Bohr, V, Kimura, M, Aviv, A, Christensen, K & Christiansen, L 2012, 'Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis', Aging Cell, bind 11, nr. 2. https://doi.org/10.1111/j.1474-9726.2011.00775.x

TY - JOUR

T1 - Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis

AU - Sørensen, Mette

AU - Thinggaard, Mikael

AU - Nygaard, Marianne

AU - Dato, Serena

AU - Tan, Qihua

AU - Hjelmborg, Jacob

AU - Andersen-Ranberg, Karen

AU - Stevnsner, Tinna V.

AU - Bohr, Vilhelm

AU - Kimura, Masayuki

AU - Aviv, Abraham

AU - Christensen, Kaare

AU - Christiansen, Lene

PY - 2012/4

Y1 - 2012/4

N2 - 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

AB - 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

KW - association study

KW - cross-sectional data and longitudinal data

KW - human longevity

KW - leukocyte telomere length

KW - telomerase reverse transcriptase

KW - telomerase RNA component

U2 - 10.1111/j.1474-9726.2011.00775.x

DO - 10.1111/j.1474-9726.2011.00775.x

M3 - Journal article

C2 - 22136229

SN - 1474-9718

VL - 11

JO - Aging Cell

JF - Aging Cell

IS - 2

ER -

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

Abstract

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