Genome-wide association study identifies common variants associated with circulating vitamin E levels

被引：118

作者：

Major, Jacqueline M.

Yu, Kai

Wheeler, William ^{[3
]}

Zhang, Hong ^{[4
]}

Cornelis, Marilyn C. ^{[5
]}

Wright, Margaret E. ^{[8
]}

Yeager, Meredith ^{[2
]}

Snyder, Kirk ^{[3
]}

Weinstein, Stephanie J.

Mondul, Alison

Eliassen, Heather ^{[9
]}

Purdue, Mark

Hazra, Aditi ^{[6
]}

McCarty, Catherine A. ^{[10
]}

Hendrickson, Sara ^{[5
,7
]}

Virtamo, Jarmo ^{[11
]}

Hunter, David ^{[5
,6
,7
]}

Chanock, Stephen

Kraft, Peter ^{[6
,7
]}

Albanes, Demetrius ^{[1
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, EPS 320, NIH, Bethesda, MD 20852 USA

[2] NCI, Core Genotyping Facil, NIH, Bethesda, MD 20852 USA

[3] Informat Management Serv Inc, Silver Spring, MD USA

[4] Fudan Univ, Sch Life Sci, Inst Biostat, Shanghai 200433, Peoples R China

[5] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[6] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[8] Univ Illinois, Dept Pathol, Chicago, IL USA

[9] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA

[10] Marshfield Clin Res Fdn, Marshfield, WI USA

[11] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 19期

基金：

美国国家卫生研究院;

关键词：

DENSITY-LIPOPROTEIN CHOLESTEROL; CLINICAL-TRIAL DATA; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; GENETIC-DETERMINANTS; ANTIOXIDANT VITAMINS; PLASMA TRIGLYCERIDES; INSULIN-RESISTANCE; LOCI; CANCER;

D O I：

10.1093/hmg/ddr296

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P = 1.7 x 10(-8)) and rs11057830 on 12q24.31 (P = 2.0 x 10(-8)) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P = 2.7 x 10(-10)). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P = 7.8 x 10(-12) (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P = 1.4 x 10(-10) (rs2108622 on 19pter-p13.11 near CYP4F2) and P = 8.2 x 10(-9) (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n = 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P < 1 x 10(-4) identified.

引用

页码：3876 / 3883

页数：8

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