title: Genetic loci associated with nonobstructive coronary artery disease in Caucasian women.
abstract: Nonobstructive coronary artery disease (CAD) in women is associated with adverse cardiovascular (CV) outcomes; however, information regarding genetic variants that predispose women to nonobstructive CAD is lacking. Women from the Women's Ischemia Syndrome Evaluation (WISE) Study and the St. James Women Take Heart (WTH) Study were genotyped with the Cardio-MetaboChip. WISE enrolled women with symptoms and signs of ischemia referred for coronary angiography; WTH enrolled asymptomatic, community-based women without heart disease. Analyses were conducted with a case (WISE)--control (WTH) design and multivariate logistic regression models to investigate genetic variation associated with likelihood of nonobstructive CAD. One genetic marker, single nucleotide polymorphism (SNP) rs2301753 on chromosome 6 in RNF39, achieved chip-wide significance for nonobstructive CAD (P < 9.5 × 10(-7)). After adjusting for baseline characteristics, we found no variants achieved chip-wide significance. However, SNP rs2301753 on chromosome 6 in RNF39 was associated with reduced likelihood of nonobstructive CAD [odds ratio (OR) 0.42 and 95% confidence interval (CI) of 0.29 to 0.68], at a nominal level of P = 5.6 × 10(-6), while SNP rs12818945 in the ATP2B1 locus on chromosome 12 was associated with increased odds for nonobstructive CAD (OR 2.38 and 95% CI of 1.63 to 3.45) and nominal P = 5.8 × 10(-6). The functions of RNF39 and ATP2B1 raise the possibility that genes involved in cardio-dysfunction may contribute to nonobstructive CAD in Caucasian women and may provide insights into novel approaches for therapy and prevention. If replicated, incorporation of these genetic variants into diagnostic evaluation may identify women at high risk for nonobstructive CAD.
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida;
authors.forename: Liming
authors.initials: L
authors.lastname: Weng
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics and Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, California;
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics and Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, California;
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland;
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Sheryl F
authors.initials: SF
authors.lastname: Kelsey
authors.affiliation: Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California;
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
authors.affiliation: Division of Cardiology, College of Medicine, University of Florida, Gainesville, Florida;
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.affiliation: Departments of Surgery and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota;
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics and Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, California;
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Medicine (Cardiology), The Ohio State University, Columbus, Ohio; and.
authors.forename: Martha
authors.initials: M
authors.lastname: Gulati
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida; Division of Cardiology, College of Medicine, University of Florida, Gainesville, Florida; dehoff@cop.ufl.edu.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
mesh_terms: D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D003710:Demography; D003971:Diastole; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D044465:White People / Q000235:genetics*
chemical_list: C506952:ATP2B1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: cardio-metabochip; genetics; nonobstructive coronary artery disease; sex