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Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study.

Donnelly LA, Palmer CN, Whitley AL, Lang CC, Doney AS, Morris AD, Donnan PT

Division of Community Health Sciences, Mackenzie Building, Kirsty Semple Way, Dundee, Scotland, UK.

BACKGROUND: Apolipoprotein E (APOE) genotypes have been associated with variations in plasma-lipid levels and with response to statins, although the influence of APOE on the response to statins remains controversial, especially in patients with diabetes. We sought to evaluate the association of the APOE genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to statins, in a large population-based cohort of patients with diabetes. METHODS AND RESULTS: A total of 1383 patients, commencing statins between 1990 and 2006, were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined both by the minimum LDLc achieved, and by the failure of the patients to reach a clinical target LDLc (< or =2 mmol/l). APOE genotype and potential confounding covariates were entered into the linear and logistic regression models. RESULTS: We found an association of APOE genotypes with both baseline and treatment responses. E2 homozygotes achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10). Minimum LDLc was associated by a linear trend with genotype. This relationship remained statistically significant after adjustment for baseline LDLc, adherence, duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10). CONCLUSION: This study demonstrates the potential clinical value of the APOE genotype as a robust marker for LDLc responses to statin drugs, which might contribute to the identification of a particularly drug-resistant subgroup of patients. This marker provides information over and above baseline lipid levels.

Published 12 March 2008 in Pharmacogenet Genomics, 18(4): 279-87.
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