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A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.

Publication ,  Journal Article
Brummett, BH; Babyak, MA; Jiang, R; Shah, SH; Becker, RC; Haynes, C; Chryst-Ladd, M; Craig, DM; Hauser, ER; Siegler, IC; Kuhn, CM; Singh, A ...
Published in: PLoS One
2013

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

12

Start / End Page

e82781

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptor, Serotonin, 5-HT2C
  • Polymorphism, Genetic
  • Male
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Female
  • Cardiovascular Diseases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brummett, B. H., Babyak, M. A., Jiang, R., Shah, S. H., Becker, R. C., Haynes, C., … Williams, R. B. (2013). A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events. PLoS One, 8(12), e82781. https://doi.org/10.1371/journal.pone.0082781
Brummett, Beverly H., Michael A. Babyak, Rong Jiang, Svati H. Shah, Richard C. Becker, Carol Haynes, Megan Chryst-Ladd, et al. “A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.PLoS One 8, no. 12 (2013): e82781. https://doi.org/10.1371/journal.pone.0082781.
Brummett BH, Babyak MA, Jiang R, Shah SH, Becker RC, Haynes C, et al. A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events. PLoS One. 2013;8(12):e82781.
Brummett, Beverly H., et al. “A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.PLoS One, vol. 8, no. 12, 2013, p. e82781. Pubmed, doi:10.1371/journal.pone.0082781.
Brummett BH, Babyak MA, Jiang R, Shah SH, Becker RC, Haynes C, Chryst-Ladd M, Craig DM, Hauser ER, Siegler IC, Kuhn CM, Singh A, Williams RB. A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events. PLoS One. 2013;8(12):e82781.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

12

Start / End Page

e82781

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptor, Serotonin, 5-HT2C
  • Polymorphism, Genetic
  • Male
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Female
  • Cardiovascular Diseases