title: A common variant in the telomerase RNA component is associated with short telomere length.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Omer T
authors.initials: OT
authors.lastname: Njajou
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Blackburn
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Damcott
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsueh
mesh_terms: 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
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase