Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

Stefan Stender; Ruth Frikke-Schmidt; Aristomenis Anestis; Dimitris Kardassis; Amar A. Sethi; Børge G Nordestgaard; Anne Tybjærg-Hansen

doi:10.1161/atvbaha.111.223867

Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

Stefan Stender, Ruth Frikke-Schmidt, Aristomenis Anestis, Dimitris Kardassis, Amar A. Sethi, Børge G Nordestgaard, Anne Tybjærg-Hansen

7 Citations (Scopus)

Abstract

Objective-Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. Methods and results-We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXRα. Homozygosity for-840AA/-115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for-840AA/-115AA did not associate with lipid or lipoprotein levels. LXRα-1830T>C (tagging the haplotype-1830C/-840A/-115A, all r0.97) associated with 91% increased transcriptional activity. Conclusion-This study suggests that functional genetic variation in LXRα predicts risk of ischemic vascular disease in the general population.

Original language	English
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	31
Issue number	12
Pages (from-to)	2990-6
Number of pages	7
ISSN	1079-5642
DOIs	https://doi.org/10.1161/atvbaha.111.223867
Publication status	Published - Dec 2011

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@article{a36928cbb1924a31a5311464d5b99b0a,

title = "Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population",

abstract = "Objective-Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. Methods and results-We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXRα. Homozygosity for-840AA/-115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for-840AA/-115AA did not associate with lipid or lipoprotein levels. LXRα-1830T>C (tagging the haplotype-1830C/-840A/-115A, all r0.97) associated with 91% increased transcriptional activity. Conclusion-This study suggests that functional genetic variation in LXRα predicts risk of ischemic vascular disease in the general population.",

author = "Stefan Stender and Ruth Frikke-Schmidt and Aristomenis Anestis and Dimitris Kardassis and Sethi, {Amar A.} and Nordestgaard, {B{\o}rge G} and Anne Tybj{\ae}rg-Hansen",

year = "2011",

month = dec,

doi = "10.1161/atvbaha.111.223867",

language = "English",

volume = "31",

pages = "2990--6",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams & Wilkins",

number = "12",

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T1 - Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

AU - Stender, Stefan

AU - Frikke-Schmidt, Ruth

AU - Anestis, Aristomenis

AU - Kardassis, Dimitris

AU - Sethi, Amar A.

AU - Nordestgaard, Børge G

AU - Tybjærg-Hansen, Anne

PY - 2011/12

Y1 - 2011/12

N2 - Objective-Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. Methods and results-We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXRα. Homozygosity for-840AA/-115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for-840AA/-115AA did not associate with lipid or lipoprotein levels. LXRα-1830T>C (tagging the haplotype-1830C/-840A/-115A, all r0.97) associated with 91% increased transcriptional activity. Conclusion-This study suggests that functional genetic variation in LXRα predicts risk of ischemic vascular disease in the general population.

AB - Objective-Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. Methods and results-We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXRα. Homozygosity for-840AA/-115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for-840AA/-115AA did not associate with lipid or lipoprotein levels. LXRα-1830T>C (tagging the haplotype-1830C/-840A/-115A, all r0.97) associated with 91% increased transcriptional activity. Conclusion-This study suggests that functional genetic variation in LXRα predicts risk of ischemic vascular disease in the general population.

U2 - 10.1161/atvbaha.111.223867

DO - 10.1161/atvbaha.111.223867

M3 - Journal article

SN - 1079-5642

VL - 31

SP - 2990

EP - 2996

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 12

ER -

Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

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