Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study

被引：51

作者：

Burdon, Kathryn P. ^{[1
,2
]}

Lehtinen, Allison B. ^{[1
,2
]}

Langefeld, Carl D. ^{[3
]}

Carr, J. Jeffrey ^{[4
]}

Rich, Stephen S. ^{[3
]}

Freedman, Barry I. ^{[5
]}

Herrington, David ^{[5
]}

Bowden, Donald W. ^{[1
,2
,5
]}

机构：

[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA

[2] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genome, Winston Salem, NC 27157 USA

[3] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA

[4] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA

[5] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA

来源：

DIABETES & VASCULAR DISEASE RESEARCH | 2008年 / 5卷 / 02期

关键词：

calcified plaque; cardiovascular disease; gene polymorphisms; type; 2; diabetes;

D O I：

10.3132/dvdr.2008.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Epoxide hydrolase is involved in metabolism of vasoactive and anti-inflammatory epoxyeicosatrienoic acids to their corresponding diols. Consequently, epoxide hydrolase 2 (EPHX2) is a candidate cardiovascular disease (CVD) gene. We investigated EPHX2 for association with subclinical CVD in European American (EA) and African American (AA) families from the Diabetes Heart Study. The R287Q polymorphism was associated with carotid artery calcified plaque (CarCP) in EAs. Other EPHX2 polymorphisms were associated with coronary artery calcified plaque (CorCP), CarCP or carotid artery intima-media thickness (IMT). Polymorphism rs7837347 was associated with all traits in the AAs (p=0.003, 0.001 and 0.017, respectively). Polymorphism rs7003694 displayed association with IMT (p=0.017) and, along with rs747276, a trend towards association with CorCP in diabetic EAs (p=0.057 and 0.080, respectively). These results provide additional evidence that EPHX2 contributes to the risk of subclinical CVD, although the true trait defining polymorphisms may not be identified and the effect size could be small.

引用

页码：128 / 134

页数：7

共 26 条

[1] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[2] Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster [J].

Bensen, JT ;

Langefeld, CD ;

Hawkins, GA ;

Green, LE ;

Mychaleckyj, JC ;

Brewer, CS ;

Kiger, DS ;

Binford, SM ;

Colicigno, CJ ;

Allred, DC ;

Freedman, BI ;

Bowden, DW .

GENOMICS, 2003, 82 (02) :194-217

[3] Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors [J].

Campbell, WB ;

Gebremedhin, D ;

Pratt, PF ;

Harder, DR .

CIRCULATION RESEARCH, 1996, 78 (03) :415-423

[4] CYTOCHROME-P450 AND THE ARACHIDONATE CASCADE [J].

CAPDEVILA, JH ;

FALCK, JR ;

ESTABROOK, RW .

FASEB JOURNAL, 1992, 6 (02) :731-736

[5] THE REACTION OF ARACHIDONIC-ACID EPOXIDES (EPOXYEICOSATRIENOIC ACIDS) WITH A CYTOSOLIC EPOXIDE HYDROLASE [J].

CHACOS, N ;

CAPDEVILA, J ;

FALCK, JR ;

MANNA, S ;

MARTINWIXTROM, C ;

GILL, SS ;

HAMMOCK, BD ;

ESTABROOK, RW .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1983, 223 (02) :639-648

[6] Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell proliferation [J].

Davis, BB ;

Thompson, DA ;

Howard, LL ;

Morisseau, C ;

Hammock, BD ;

Weiss, RH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2222-2227

[7] Efficiency and power in genetic association studies [J].

de Bakker, PIW ;

Yelensky, R ;

Pe'er, I ;

Gabriel, SB ;

Daly, MJ ;

Altshuler, D .

NATURE GENETICS, 2005, 37 (11) :1217-1223

[8] The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke [J].

Fornage, M ;

Lee, CR ;

Doris, PA ;

Bray, MS ;

Heiss, G ;

Zeldin, DC ;

Boerwinkle, E .

HUMAN MOLECULAR GENETICS, 2005, 14 (19) :2829-2837

[9] Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects - The Coronary Artery Risk Development in Young Adults (CARDIA) study [J].

Fornage, M ;

Boerwinkle, E ;

Doris, PA ;

Jacobs, D ;

Liu, K ;

Wong, ND .

CIRCULATION, 2004, 109 (03) :335-339

[10] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

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