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Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence - 18/04/17

Doi : 10.1016/j.ahj.2016.12.013 
Redford B. Williams, MD a, , George D. Bishop, PhD b, c, Brett C. Haberstick, PhD d, Andrew Smolen, PhD d, Beverly H. Brummett, PhD a, Ilene C. Siegler, PhD a, Michael A. Babyak, PhD a, Xiaodong Zhang, PhD a, e, f, E. Shyong Tai, PhD g, h, Jeannette Jen-Mai Lee, PhD g, Maudrene Tan, PhD g, Yik Ying Teo, PhD g, i, Shiwei Cai, PhD e, f, Edmund Chan, PhD g, Carolyn Tucker Halpern, PhD j, k, Eric A. Whitsel, MD l, m, Shawn Bauldry, PhD n, Kathleen Mullan Harris, PhD k, o
a Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA 
b Yale-NUS College, Singapore, Singapore 
c Department of Psychology, National University of Singapore, Singapore 
d Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA 
e Neuroscience & Behavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore 
f Department of Physiology, National University of Singapore, Singapore 
g Saw Swee Hock School of Public Health, National University of Singapore, Singapore 
h Department of Medicine, National University of Singapore, Singapore 
i Department of Statistics and Applied Probability, National University of Singapore 
j Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA 
k Carolina Population Center, University of North Carolina at Chapel Hill, NC, USA 
l Department of Epidemiology, University of North Carolina, Gillings School of Global Public Health, Chapel Hill, USA 
m Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, NC, USA 
n Department of Sociology, University of Alabama, Birmingham, AL, USA 
o Department of Sociology, University of North Carolina, Chapel Hill, USA 

Reprint requests: Redford B. Williams, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamNCUSA

Background

Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore.

Methods

Logistic regression and linear models tested associations between triallelic (L′S′, based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N=11,815) in 2008–09 and during 2004–07 in 4196 Singaporeans.

Results

In US Whites, L′ allele carriers had higher SBP (0.9 mm Hg, 95% CI=0.26-1.56) and greater odds (OR=1.23, 95% CI=1.10-1.38) of more severe hypertension than those with S′S′ genotypes. In African Americans, L′ carriers had lower mean SBP (−1.27mm Hg, 95% CI=−2.53 to −0.01) and lower odds (OR = 0.78, 95% CI=0.65-0.94) of more severe hypertension than those with the S′S′ genotype. In African Americans, those with L′L′ genotypes had lower DBP (−1.13mm Hg, 95% CI=−2.09 to −0.16) than S′ carriers. In Native Americans, L′ carriers had lower SBP (−6.05mm Hg, 95% CI=−9.59 to −2.51) and lower odds of hypertension (OR = 0.34, 95% CI=0.13-0.89) than those with the S′S′ genotype. In Asian/Pacific Islanders those carrying the L′ allele had lower DBP (−1.77mm Hg, 95% CI=−3.16 to −0.38) and lower odds of hypertension (OR = 0.68, 95% CI=0.48-0.96) than those with S′S′. In the Singapore sample S′ carriers had higher SBP (3.02mm Hg, 95% CI=0.54-5.51) and DBP (1.90mm Hg, 95% CI=0.49-3.31) than those with the L′L′ genotype.

Conclusions

These findings suggest that Whites carrying the L′ allele, African Americans and Native Americans with the S′S′ genotype, and Asians carrying the S′ allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures.

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