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A genetic risk scor...
A genetic risk score is significantly associated with statin therapy response in the elderly population
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- Ciuculete, Diana-Maria (author)
- Uppsala universitet,Funktionell farmakologi
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- Bandstein, Marcus, 1988- (author)
- Uppsala universitet,Funktionell farmakologi
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- Benedict, Christian (author)
- Uppsala universitet,Funktionell farmakologi
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- Waeber, G. (author)
- Univ Hosp Lausanne CHUV, Dept Internal Med, Lausanne, Switzerland.
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- Vollenweider, P. (author)
- Univ Hosp Lausanne CHUV, Dept Internal Med, Lausanne, Switzerland.
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- Lind, Lars (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Schiöth, Helgi B. (author)
- Uppsala universitet,Funktionell farmakologi
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- Mwinyi, Jessica (author)
- Uppsala universitet,Funktionell farmakologi
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(creator_code:org_t)
- 2016-12-12
- 2017
- English.
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In: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 91:3, s. 379-385
- Related links:
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https://rss.onlineli...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- pharmacogenetics
- polygenetic risk score
- random forest analysis
- single nucleotide polymorphism
- statins
Publication and Content Type
- ref (subject category)
- art (subject category)
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