Robert Y L Zee1, Paul M Ridker, Daniel I Chasman. 1. Division of Preventive Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02215, USA. rzee@rics.bwh.harvard.edu
Abstract
OBJECTIVE: Leukocyte telomere length shortening has recently been associated with type 2 diabetes mellitus (T2D). Whether this observation was modulated by genetic variation within the telomere-pathway genes remains elusive. To date, no prospective epidemiological data on the relationship of telomere-pathway gene variation with T2D are available. METHODS: The association between 150 tagging-SNPs (tSNPs) of 11 telomere-pathway genes (TERC, UCP1, TERT, POT1, TNKS, TERF1, TNKS2, TEP1, ACD, TERF2 and TERF2IP) and incident T2D was investigated in 22,715 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cardiovascular disease, cancer and diabetes at baseline. During a 13-year follow-up period, 1445 participants developed an incident T2D. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2D risk assuming an additive genetic model. Haplotype block analysis was also performed. RESULTS: A total of eleven tSNPs within TERF1, TNKS, TEP1, ACD, and TERF2 were associated with T2D risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis again revealed an association of several prespecified haplotypes of TERF1, and TEP1 with T2D risk (all p-uncorrected <0.040). CONCLUSION: If corroborated in other prospective studies, the present findings suggest that genetic variation within the telomere-pathway gene loci examined may be useful predictor for T2D risk assessment.
OBJECTIVE: Leukocyte telomere length shortening has recently been associated with type 2 diabetes mellitus (T2D). Whether this observation was modulated by genetic variation within the telomere-pathway genes remains elusive. To date, no prospective epidemiological data on the relationship of telomere-pathway gene variation with T2D are available. METHODS: The association between 150 tagging-SNPs (tSNPs) of 11 telomere-pathway genes (TERC, UCP1, TERT, POT1, TNKS, TERF1, TNKS2, TEP1, ACD, TERF2 and TERF2IP) and incident T2D was investigated in 22,715 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cardiovascular disease, cancer and diabetes at baseline. During a 13-year follow-up period, 1445 participants developed an incident T2D. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2D risk assuming an additive genetic model. Haplotype block analysis was also performed. RESULTS: A total of eleven tSNPs within TERF1, TNKS, TEP1, ACD, and TERF2 were associated with T2D risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis again revealed an association of several prespecified haplotypes of TERF1, and TEP1 with T2D risk (all p-uncorrected <0.040). CONCLUSION: If corroborated in other prospective studies, the present findings suggest that genetic variation within the telomere-pathway gene loci examined may be useful predictor for T2D risk assessment.
Authors: T Nishikawa; D Edelstein; X L Du; S Yamagishi; T Matsumura; Y Kaneda; M A Yorek; D Beebe; P J Oates; H P Hammes; I Giardino; M Brownlee Journal: Nature Date: 2000-04-13 Impact factor: 49.962
Authors: Klelia D Salpea; Philippa J Talmud; Jackie A Cooper; Cecilia G Maubaret; Jeffrey W Stephens; Kavin Abelak; Steve E Humphries Journal: Atherosclerosis Date: 2009-10-06 Impact factor: 5.162
Authors: Paul M Ridker; Daniel I Chasman; Robert Y L Zee; Alex Parker; Lynda Rose; Nancy R Cook; Julie E Buring Journal: Clin Chem Date: 2007-12-10 Impact factor: 8.327
Authors: Mengmeng Du; Jennifer Prescott; Marilyn C Cornelis; Susan E Hankinson; Edward Giovannucci; Peter Kraft; Immaculata De Vivo Journal: PLoS One Date: 2013-02-12 Impact factor: 3.240
Authors: Cécilia G Maubaret; Klelia D Salpea; Casey E Romanoski; Lasse Folkersen; Jackie A Cooper; Coralea Stephanou; Ka Wah Li; Jutta Palmen; Anders Hamsten; Andrew Neil; Jeffrey W Stephens; Aldons J Lusis; Per Eriksson; Philippa J Talmud; Steve E Humphries Journal: PLoS One Date: 2013-12-12 Impact factor: 3.240
Authors: Peter Willeit; Julia Raschenberger; Emma E Heydon; Sotirios Tsimikas; Margot Haun; Agnes Mayr; Siegfried Weger; Joseph L Witztum; Adam S Butterworth; Johann Willeit; Florian Kronenberg; Stefan Kiechl Journal: PLoS One Date: 2014-11-12 Impact factor: 3.240
Authors: Anna-Lena Volckmar; Chung Ting Han; Carolin Pütter; Stefan Haas; Carla I G Vogel; Nadja Knoll; Christoph Struve; Maria Göbel; Katharina Haas; Nikolas Herrfurth; Ivonne Jarick; Harald Grallert; Annette Schürmann; Hadi Al-Hasani; Johannes Hebebrand; Sascha Sauer; Anke Hinney Journal: PLoS One Date: 2016-02-01 Impact factor: 3.240