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PLoS One. 2013 Dec 12;8(12):e83122. doi: 10.1371/journal.pone.0083122. eCollection 2013.

Association of TERC and OBFC1 haplotypes with mean leukocyte telomere length and risk for coronary heart disease.

Author information

1
Cardiovascular Genetics, BHF Laboratories,University College London (UCL), London, United Kingdom ; ISPED, Université Bordeaux Ségalen/INSERM u.897, Bordeaux, France.
2
Cardiovascular Genetics, BHF Laboratories,University College London (UCL), London, United Kingdom ; Institute of Molecular Biology & Genetics, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
3
Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
4
Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
5
Cardiovascular Genetics, BHF Laboratories,University College London (UCL), London, United Kingdom.
6
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
7
Division Public Health & Primary Health Care, University of Oxford, Oxford, United Kingdom.
8
Diabetes Research Group, School of Medicine, Swansea University, Swansea, United Kingdom.

Abstract

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 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) 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 (β=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.

PMID:
24349443
PMCID:
PMC3861448
DOI:
10.1371/journal.pone.0083122
[Indexed for MEDLINE]
Free PMC Article
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