Abstract
Telomerase is of key importance for telomere maintenance and variants of the genes encoding its major subunits, TERT and TERC, are candidates for inter-individual 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 (HR (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.