Abstract:
: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.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Ciuculete DM,Bandstein M,Benedict C,Waeber G,Vollenweider P,Lind L,Schiöth HB,Mwinyi Jdoi
10.1111/cge.12890subject
Has Abstractpub_date
2017-03-01 00:00:00pages
379-385issue
3eissn
0009-9163issn
1399-0004journal_volume
91pub_type
杂志文章abstract::Two brothers, products of a consanguineous marriage, had severe hypoplastic genitalia and cardiomyopathy. These findings are similar to those of three other brothers of another consanguineous family who in addition had evidence of mental retardation. These five boys probably represent a previously undescribed syndrome...
journal_title:Clinical genetics
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doi:10.1111/j.1399-0004.1984.tb01073.x
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journal_title:Clinical genetics
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doi:10.1111/j.1399-0004.1981.tb01821.x
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
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journal_title:Clinical genetics
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00855.x
更新日期:2007-09-01 00:00:00
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journal_title:Clinical genetics
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:1985-06-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章,评审
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journal_title:Clinical genetics
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13541
更新日期:2019-07-01 00:00:00
abstract::Mutations in the NPC1 or NPC2 gene are responsible for Niemann-Pick type C (NPC) disease (OMIM #257220), an autosomal recessive neurodegenerative lysosomal storage disorder caused by an incorrect regulation of intracellular lipid trafficking. A molecular analysis carried out in 30 unrelated patients identified 43 dist...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01504.x
更新日期:2011-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2019-05-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
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更新日期:2002-06-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
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更新日期:2007-01-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1978.tb02057.x
更新日期:1978-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2019-06-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1977.tb00950.x
更新日期:1977-12-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01066.x
更新日期:1984-10-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.12519
更新日期:2015-08-01 00:00:00