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

• Published in: The American heart journal Vol. 185; pp. 110 - 122
• Main Authors: Williams, Redford B, Bishop, George D, Haberstick, Brett C, Smolen, Andrew, Brummett, Beverly H, Siegler, Ilene C, Babyak, Michael A, Zhang, Xiaodong, Tai, E Shyong, Lee, Jeannette Jen-Mai, Tan, Maudrene, Teo, Yik Ying, Cai, Shiwei, Chan, Edmund, Halpern, Carolyn Tucker, Whitsel, Eric A, Bauldry, Shawn, Harris, Kathleen Mullan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017; Elsevier Limited
• Subjects: Adult; Alleles; Asian People - genetics; Black or African American - genetics; Blood pressure; Blood Pressure - genetics; Cardiovascular; Cardiovascular diseases; Coronary vessels; Female; Gene Frequency; Gene polymorphism; Genes; Genomes; Genotype; Genotypes; Haplotypes; Health risk assessment; Health risks; Heart attacks; Humans; Hypertension; Hypertension - epidemiology; Hypertension - ethnology; Hypertension - genetics; Hypotheses; Indians, North American - genetics; Laboratories; Linear Models; Logistic Models; Male; Middle Aged; Minority & ethnic groups; Mortality; Native Americans; Nervous system; Odds Ratio; Polymorphism; Population; Psychiatry; Racial differences; Serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin transporter; Singapore - epidemiology; Stress; Stroke; Studies; Transporter; United States - epidemiology; Veins & arteries; White People - genetics; United States; Singapore
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2016.12.013

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 two large, nationally representative samples in the U.S. 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 U.S. Whites L’ allele carriers had higher SBP (0.9 mmHg, 95%CI = 0.26, 1.56) and greater odds (odds ratio [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 (−1.27 mmHg, 95% CI = −2.53, −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 (−1.13 mmHg, 95% CI = −2.09, −0.16) than S′ carriers. In Native Americans, L’ carriers had lower SBP (−6.05 mmHg, 95% CI = −9.59, −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 (−1.77 mmHg, 95%CI = −3.16,-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 (3.02 mmHg, 95%CI = 0.54, 5.51) and DBP (1.90 mmHg, 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.