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A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study

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A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study. / Donnelly, Louise A.; Doney, Alex S. F.; Dannfald, Jennifer; Whitley, Adrian L.; Lang, Chim C.; Morris, Andrew D.; Donnan, Peter T.; Palmer, Colin N. A.

In: Pharmacogenetics and Genomics, Vol. 18, No. 12, 12.2008, p. 1021-1026.

Research output: Contribution to journalArticle

Harvard

Donnelly, LA, Doney, ASF, Dannfald, J, Whitley, AL, Lang, CC, Morris, AD, Donnan, PT & Palmer, CNA 2008, 'A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study' Pharmacogenetics and Genomics, vol 18, no. 12, pp. 1021-1026.

APA

Donnelly, L. A., Doney, A. S. F., Dannfald, J., Whitley, A. L., Lang, C. C., Morris, A. D., Donnan, P. T., & Palmer, C. N. A. (2008). A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study. Pharmacogenetics and Genomics, 18(12), 1021-1026

Vancouver

Donnelly LA, Doney ASF, Dannfald J, Whitley AL, Lang CC, Morris AD et al. A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study. Pharmacogenetics and Genomics. 2008 Dec;18(12):1021-1026.

Author

Donnelly, Louise A.; Doney, Alex S. F.; Dannfald, Jennifer; Whitley, Adrian L.; Lang, Chim C.; Morris, Andrew D.; Donnan, Peter T.; Palmer, Colin N. A. / A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study.

In: Pharmacogenetics and Genomics, Vol. 18, No. 12, 12.2008, p. 1021-1026.

Research output: Contribution to journalArticle

Bibtex - Download

@article{cc69f7acd22244c2a4cd394d873fe08e,
title = "A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study",
author = "Donnelly, {Louise A.} and Doney, {Alex S. F.} and Jennifer Dannfald and Whitley, {Adrian L.} and Lang, {Chim C.} and Morris, {Andrew D.} and Donnan, {Peter T.} and Palmer, {Colin N. A.}",
year = "2008",
volume = "18",
number = "12",
pages = "1021--1026",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A paucimorphic variant in the HMO-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study

A1 - Donnelly,Louise A.

A1 - Doney,Alex S. F.

A1 - Dannfald,Jennifer

A1 - Whitley,Adrian L.

A1 - Lang,Chim C.

A1 - Morris,Andrew D.

A1 - Donnan,Peter T.

A1 - Palmer,Colin N. A.

AU - Donnelly,Louise A.

AU - Doney,Alex S. F.

AU - Dannfald,Jennifer

AU - Whitley,Adrian L.

AU - Lang,Chim C.

AU - Morris,Andrew D.

AU - Donnan,Peter T.

AU - Palmer,Colin N. A.

PY - 2008/12

Y1 - 2008/12

N2 - <p>Background Considerable interindividual variation exists in cholesterol-lowering response to 3-hydroxy-3methylglutaryl coenzyme A reductase (HMGCR) inhibitors (statins). HMGCR catalyzes the rate-limiting step in cholesterol biosynthesis, and also plays a significant role in cholesterol homeostasis. We evaluated the association of a single nucleotide polymorphism (rs17238540) in the HMGCR gene with lipid-lowering response to statins in a large population-based cohort of patients with diabetes.</p><p>Methods One thousand six hundred and one patients commencing statins between 1993 and 2006 were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined by both percentage change in lipids, and whether patients failed to reach a total cholesterol target of less than or equal to 4 mmol/l. Covariates included HMGCR genotype, baseline lipids, age, sex, adherence and statin dose. All patients were genotyped for rs17238540 using a TAQMAN-based allelic discrimination assay.</p><p>Results Twenty-eight percent of individuals homozygous for the more frequent T allele failed to reach target compared with 51% of the individuals with a single copy of the minor G allele (carrier frequency 3.3%), with an adjusted odds ratio (95% confidence interval) for failure of 2.93 (1.61-5.34) mmol/l, P=0.0005. In addition, we found that the heterozygotes had a 13% smaller reduction in total cholesterol (-32.3 vs. -371%, P=0.0081) and a 27% smaller reduction in triglycerides 275 vs. -37.6%, P=0.0046).</p><p>Conclusion Individuals heterozygous for the G allele of rs17238540 in the HMGCR gene may respond less well to statin therapy in terms of total cholesterol and triglyceride lowering. Pharmacogenetics and Genomics 18:1021-1026 (C) 2008 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins.</p>

AB - <p>Background Considerable interindividual variation exists in cholesterol-lowering response to 3-hydroxy-3methylglutaryl coenzyme A reductase (HMGCR) inhibitors (statins). HMGCR catalyzes the rate-limiting step in cholesterol biosynthesis, and also plays a significant role in cholesterol homeostasis. We evaluated the association of a single nucleotide polymorphism (rs17238540) in the HMGCR gene with lipid-lowering response to statins in a large population-based cohort of patients with diabetes.</p><p>Methods One thousand six hundred and one patients commencing statins between 1993 and 2006 were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined by both percentage change in lipids, and whether patients failed to reach a total cholesterol target of less than or equal to 4 mmol/l. Covariates included HMGCR genotype, baseline lipids, age, sex, adherence and statin dose. All patients were genotyped for rs17238540 using a TAQMAN-based allelic discrimination assay.</p><p>Results Twenty-eight percent of individuals homozygous for the more frequent T allele failed to reach target compared with 51% of the individuals with a single copy of the minor G allele (carrier frequency 3.3%), with an adjusted odds ratio (95% confidence interval) for failure of 2.93 (1.61-5.34) mmol/l, P=0.0005. In addition, we found that the heterozygotes had a 13% smaller reduction in total cholesterol (-32.3 vs. -371%, P=0.0081) and a 27% smaller reduction in triglycerides 275 vs. -37.6%, P=0.0046).</p><p>Conclusion Individuals heterozygous for the G allele of rs17238540 in the HMGCR gene may respond less well to statin therapy in terms of total cholesterol and triglyceride lowering. Pharmacogenetics and Genomics 18:1021-1026 (C) 2008 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins.</p>

KW - diabetes mellitus

KW - 3-hydroxy-3-methylglutaryl coenzyme A reductase

KW - lipoproteins

KW - statins

KW - CORONARY-HEART-DISEASE

KW - DENSITY-LIPOPROTEIN CHOLESTEROL

KW - APOLIPOPROTEIN-E GENOTYPES

KW - TRANSFER PROTEIN GENE

KW - COENZYME-A REDUCTASE

KW - PREVENTION

KW - THERAPY

KW - ATORVASTATIN

KW - SIMVASTATIN

KW - PLASMA

M1 - Article

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 12

VL - 18

SP - 1021

EP - 1026

ER -

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