A common variant in the telomerase RNA component is associated with short telomere length.
BACKGROUND
Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS).


METHODS
Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.


RESULTS
The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = -0.19±0.04 kbp, p = 0.001).


CONCLUSIONS
Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis.
Njajou
Omer T
OT
Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
Blackburn
Elizabeth H
EH
Pawlikowska
Ludmila
L
Mangino
Massimo
M
Damcott
Coleen M
CM
Kwok
Pui-Yan
PY
Spector
Timothy D
TD
Newman
Anne B
AB
Harris
Tamara B
TB
Cummings
Steven R
SR
Cawthon
Richard M
RM
Shuldiner
Alan R
AR
Valdes
Ana M
AM
Hsueh
Wen-Chi
WC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D001823:Body Composition; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014427:Twins / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics; D055815:Young Adult
C422952:telomerase RNA; D012313:RNA; D019098:Telomerase