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2. Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease

Author

Maubaret, CG, Salpea, KD, Romanoski, CE, Folkersen, L, Cooper, JA, Stephanou, C, Li, KW, Palmen, J, Hamsten, A, Neil, A, Stephens, JW, Lusis, AJ, Eriksson, P, Talmud, PJ, Humphries, SE, Juhan Vague, I, Margaglione, M, Yudkin, J, Tremoli, E, St J. O'Reilly, D, Cambien, F, De Backer, G, Rosseneu, M, Shepherd, J, Tiret, L, Menzel, HJ, De Henauw, S, Faergeman, O, Gerdes, C, Saava, M, Aasvee, K, Ehnholm, C, Elovainio, R, Peräsalo, J, Kesäniemi, YA, Savolainen, MJ, Palomaa, P, Nicaud, V, Poirier, O, Visvikis, S, Fruchart, JC, Dallongeville, J, Beisiegel, U, Dingler, C, Tsitouris, G, Papageorgakis, N, Kolovou, G, Farinaro, E, Havekes, LM, Halpern, MJ, Canena, J, Masana, L, Ribalta, J, Jammoul, A, LaVille, A, Gutzwiller, F, Martin, B, Murphy, M, Gudnason, V, Fisher, RM, Stansbie, D, Day, AP, Edgar, M, Kee, F, Evans, A, Hurel, SJ, Broome, S, Seed, M, Betteridge, DJ, Cooper, J, Humphrie, SE, Durrington, PN, Thompson, GR, Neil, HA, DI MINNO, GIOVANNI, BHF Laboratories, Rayne building, University College of London [London] (UCL), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Biomedical Sciences Research Center, Al. Fleming, Department of Human Genetics, UCLA, University of California [Los Angeles] (UCLA), University of California-University of California-Semel Institute, Karolinska Institutet [Stockholm], Division Public Health and Primary Health Care [Oxford], University of Oxford [Oxford], School of Medicine, Swansea University, Maubaret, Cg, Salpea, Kd, Romanoski, Ce, Folkersen, L, Cooper, Ja, Stephanou, C, Li, Kw, Palmen, J, Hamsten, A, Neil, A, Stephens, Jw, Lusis, Aj, Eriksson, P, Talmud, Pj, Humphries, Se, Juhan Vague, I, Margaglione, M, DI MINNO, Giovanni, Yudkin, J, Tremoli, E, St J. O'Reilly, D, Cambien, F, De Backer, G, Rosseneu, M, Shepherd, J, Tiret, L, Menzel, Hj, De Henauw, S, Faergeman, O, Gerdes, C, Saava, M, Aasvee, K, Ehnholm, C, Elovainio, R, Peräsalo, J, Kesäniemi, Ya, Savolainen, Mj, Palomaa, P, Nicaud, V, Poirier, O, Visvikis, S, Fruchart, Jc, Dallongeville, J, Beisiegel, U, Dingler, C, Tsitouris, G, Papageorgakis, N, Kolovou, G, Farinaro, E, Havekes, Lm, Halpern, Mj, Canena, J, Masana, L, Ribalta, J, Jammoul, A, Laville, A, Gutzwiller, F, Martin, B, Murphy, M, Gudnason, V, Fisher, Rm, Stansbie, D, Day, Ap, Edgar, M, Kee, F, Evans, A, Hurel, Sj, Broome, S, Seed, M, Betteridge, Dj, Cooper, J, Humphrie, Se, Durrington, Pn, Thompson, Gr, and Neil, Ha

Subjects
Male, Telomere-Binding Proteins, lcsh:Medicine, Coronary Disease, Genome-wide association study, Single-nucleotide polymorphism, Locus (genetics), Biology, Lower risk, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Leukocytes, Humans, SNP, Allele, lcsh:Science, Telomerase, Aged, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, lcsh:R, Haplotype, Telomere Homeostasis, Middle Aged, Telomere, 3. Good health, Minor allele frequency, Diabetes Mellitus, Type 2, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, RNA, lcsh:Q, Female, Research Article
Abstract

International audience; 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.

Published
2013
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3. Introduction

Author

Thompson Gr

Subjects
biology, Cholesterol, Pharmacology, Coronary disease, Cholesterol blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors, chemistry.chemical_compound, chemistry, Hypolipidemic Agents, HMG-CoA reductase, biology.protein, Lipid lowering, Sociology, Cardiology and Cardiovascular Medicine
Published
1991
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5. Experience with plasma-exchange in homozygous familial hypercholesterolaemia

Author

POSTIGLIONE, ALFREDO, Thompson GR, Postiglione, Alfredo, and Thompson, Gr

Subjects
Hyperlipoproteinemia Type II, Cholesterol, Plasma Exchange, Platelet Count, Homozygote, Humans, Blood Viscosity, Blood Coagulation, Apolipoproteins B
Abstract

Reduction of plasma cholesterol and apolipoprotein B concentrations can be expected and may appear to slow the rate of progression of the atherosclerotic process (Thompson, 1980). The usefulness of plasma exchange to the treatment of homozygous FH patients has been extended recently by Stoffel et al. (1981), who perfused plasma through an on-line anti-LDL sepharose column, which selectively removes LDL. Having theoretical advantages over plasma-exchange, this procedure avoids the loss of HDL and of other important plasma proteins. In short, plasma-exchange has proved to be a remarkably safe, well tolerated and effective means of treating homozygous FH.

Published
1985

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