A Common Variant in the Telomerase RNA Component Is Associated with Short Telomere Length

• Published in: PloS one Vol. 5; no. 9; p. e13048
• Main Authors: Njajou, Omer T., Blackburn, Elizabeth H., Pawlikowska, Ludmila, Mangino, Massimo, Damcott, Coleen M., Kwok, Pui-Yan, Spector, Timothy D., Newman, Anne B., Harris, Tamara B., Cummings, Steven R., Cawthon, Richard M., Shuldiner, Alan R., Valdes, Ana M., Hsueh, Wen-Chi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.09.2010; Public Library of Science (PLoS)
• Subjects: Activities of daily living; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Aging - genetics; Aging - metabolism; Alleles; Analysis; Biocompatibility; Biology; Biomedical materials; Body Composition; Body composition (biology); Cardiovascular disease; Carriers; Chromosomes; Cohort Studies; Committees; Consent; Diabetes; Endocrinology; Enzymes; Epidemiology; European Continental Ancestry Group - genetics; Female; Gene frequency; Genetic Variation; Genetics and Genomics; Genetics and Genomics/Complex Traits; Genetics and Genomics/Medical Genetics; Health; Homeostasis; Hospitals; Humans; Laboratories; Male; Medicine; Middle Aged; Mutation; Osteoporosis; Osteoporosis - genetics; Osteoporosis - metabolism; Physiological aspects; Polymorphism, Single Nucleotide; Population; Population genetics; Regression analysis; Regression models; Ribonucleic acid; RNA; RNA - genetics; RNA - metabolism; Single-nucleotide polymorphism; Statistical analysis; Statistical methods; Stem cells; Studies; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomere - genetics; Telomere - metabolism; Telomeres; Trends; Twins - genetics; Twins - metabolism; Variance analysis; Womens health; Young Adult; San Francisco California; California; Pittsburgh Pennsylvania; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013048

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). 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. 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). 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.