Genetic loci associated with nonobstructive coronary artery disease in Caucasian women

Liming Weng, Kent D. Taylor, Yii Der Ida Chen, George Sopko, Sheryl F. Kelsey, C. Noel Bairey Merz, Carl J. Pepine, Virginia M. Miller, Jerome I. Rotter, Martha Gulati, Mark O. Goodarzi, Rhonda M. Cooper-DeHoff

Research output: Contribution to journalArticle

8 Scopus citations

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 RNF39and 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.

Original languageEnglish (US)
Pages (from-to)12-20
Number of pages9
JournalPhysiological Genomics
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Cardio-metabochip
  • Genetics
  • Nonobstructive coronary artery disease
  • Sex

ASJC Scopus subject areas

  • Physiology
  • Genetics

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    Weng, L., Taylor, K. D., Chen, Y. D. I., Sopko, G., Kelsey, S. F., Bairey Merz, C. N., Pepine, C. J., Miller, V. M., Rotter, J. I., Gulati, M., Goodarzi, M. O., & Cooper-DeHoff, R. M. (2016). Genetic loci associated with nonobstructive coronary artery disease in Caucasian women. Physiological Genomics, 48(1), 12-20. https://doi.org/10.1152/physiolgenomics.00067.2015