ArticlePharmacogenetics and genomics2011
Liver X receptor α gene polymorphisms and variable cardiovascular outcomes in patients treated with antihypertensive therapy: results from the INVEST-GENES study.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 23 citations in OpenAlex.
- Pharmacogenetic association of theFrontiers in pharmacology · 2023Article
- ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients.BMC medical genetics · 2018Article
- Liver X Receptor-α polymorphisms (rs11039155 and rs2279238) are associated with susceptibility to vitiligo.Meta gene · 2016Article
- Hypertension pharmacogenomics: in search of personalized treatment approaches.Nature reviews. Nephrology · 2016Review
- Associations of lipid levels susceptibility loci with coronary artery disease in Chinese population.Lipids in health and disease · 2015Article
- Article
- Genetic variations in SREBP-1 and LXRα are not directly associated to PCOS but contribute to the physiological specifics of the syndrome.Molecular biology reports · 2012Article
- Review
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7 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsLiver X receptor-α (LXRA) is a nuclear receptor that regulates genes important in cholesterol homeostasis and inflammation. Several single nucleotide polymorphisms (SNPs) in the LXRA gene (NR1H3) have been earlier associated with metabolic phenotypes (dyslipidemia and elevated body mass index). Metabolic dysregulation is a major contributor to coronary disease; therefore, we assessed LXRA in International Verapamil Sustained Release SR Trandolapril Study Genetic Substudy (INVEST-GENES), a genetic-substudy of a large clinical trial in patients with hypertension and coronary artery disease.
methodsSeven tag SNPs in the LXRA gene region (NR1H3) were selected for study: rs11039149, rs12221497, rs2279238, rs7120118, rs326213, rs11039159, and rs10501321. One thousand fifty-nine patients were genotyped from the INVEST-GENES case-control set (verapamil-sustained release-based or atenolol-based treatment strategies) that comprised of 297 cases frequency matched (approximately 2.5:1) with that of event-free controls by sex and race. The primary outcome was defined as first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Adjusted odds ratios (ORs) were calculated using logistic regression.
resultsThree of the seven SNPs were associated with significant effects on the primary outcome in nonBlacks. The variant G allele of rs11039149 and the variant A allele of rs12221497 were associated with reduced risk of experiencing the primary outcome [OR: 0.62, confidence interval (CI): 0.45-0.85, P=0.003 and OR: 0.60, CI: 0.39-0.91, P=0.016, respectively]. The rs2279238 genotype was associated with a significant increase in risk for the primary outcome (OR: 1.42, CI: 1.03-1.95, P=0.03). Furthermore, there was a significant genotype-treatment strategy interaction for carriers of the variant T allele of rs2279238 (OR for verapamil-sustained release strategy compared with atenolol strategy: 2.86, CI: 1.50-5.46, P=0.0015). Diplotype analyses showed that the SNPs are rarely coinherited and support the directionally opposite effects of the SNPs on the primary outcome.
conclusionLXRA genotypes were associated with variable risk for cardiovascular outcomes and pharmacogenetic effect in INVEST-GENES. These novel findings suggest that LXRA is a genetic/pharmacogenetic target that should be further explored.
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