Autor segons l'article: Maubaret, Cecilia G.; Salpea, Klelia D.; Romanoski, Casey E.; Folkersen, Lasse; Cooper, Jackie A.; Stephanou, Coralea; Li, Ka Wah; Palmen, Jutta; Hamsten, Anders; Neil, Andrew; Stephens, Jeffrey W.; Lusis, Aldons J.; Eriksson, Per; Talmud, Philippa J.; Humphries, Steve E.;Simon Broome Res Grp; EARSII Consortium
Departament: Medicina i Cirurgia
Autor/s de la URV: Ribalta Vives, Josep
Paraules clau: Susceptibility Myocardial-infarction Loci Interleukin-6 gene Genotype Genome-wide association Functional polymorphism Common variants Cardiovascular-disease Atherosclerosis
Resum: Objective: To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.
Methods: Four SNPs at three loci BICD1 (rs2630578 G gamma C), 18q12.2 (rs2162440 G gamma T), and OBFC1 (rs10786775 C gamma G, rs11591710 A gamma C) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 C gamma G, rs10936601G>T and rs16847897 G gamma C) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.
Results: Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (beta=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61-0.97; P=0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61-0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.
Conclusion: Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.
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Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 19326203
Adreça de correu electrònic de l'autor: josep.ribalta@urv.cat
Identificador de l'autor: 0000-0002-8879-4719
Data d'alta del registre: 2023-02-18
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083122
Referència a l'article segons font original: Plos One. 8 (12): e83122-
Referència de l'ítem segons les normes APA: Maubaret, Cecilia G.; Salpea, Klelia D.; Romanoski, Casey E.; Folkersen, Lasse; Cooper, Jackie A.; Stephanou, Coralea; Li, Ka Wah; Palmen, Jutta; Hams (2013). Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease. Plos One, 8(12), e83122-. DOI: 10.1371/journal.pone.0083122
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI de l'article: 10.1371/journal.pone.0083122
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2013
Tipus de publicació: Journal Publications
Repositori URV