Association between serotonin 2A receptor (HTR2A) genetic variations and risk of hypertension in a community-based cohort study

Abstract

Background: Hypertension is one of the risk factors for obesity-related cardiovascular diseases. We investigated whether genetic variations in serotonin 2A receptor (HTR2A) were associated with hypertension. Methods: We carried out a cross-sectional study in cohorts A (Ansan-Ansung cohort, N = 6039) and B (Wonju-Pyengchang cohort, N = 7524). Several genetic variants in HTR2A including rs7330636, rs9590999, rs2183057, and rs4942595 were selected and genotyped. Results: In hypertensive participants in cohort A, the baseline systolic blood pressure and body mass index were 141.80 ± 17.20 mg/dL and 24.48 ± 4.75 kg/m 2 , respectively, which were higher than in those without hypertension (p < 0.001). rs4942595TC genotype was associated with hypertension in cohort A (OR = 0.739), after adjusting for variables. Subjects with rs4942578AA genotype had a decreased risk of hypertension after adjusting for clinical factor (OR = 0.735) in cohort B, and an elevated risk of hypertension in cohort A (OR = 1.562). The logistic regression analysis showed that participants with rs4941573TC genotype were 1.327 times more likely to have a higher blood pressure than those with TT genotype (95% CI 1.101-1.599) in cohort B. Whereas, the OR for developing hypertension in subjects with rs17069883CC genotype compared to those with AA genotype was 1.447 (95% CI 1.018-2.056; p for trend = 0.040) in cohort A. Conclusions: HTR2A genetic variations were associated with hypertension risk in our study.

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

“…In a previous study, L3/L4 methylation in the placenta was found to be related to neonatal attention and the quality of movement, neurobehavioral measures that may predict future attention, anxiety, and motor development [ 50 ]. In addition, alterations in L3 and/or L4 methylation in various tissues, including peripheral blood [ 40 , 43 , 44 ], saliva [ 54 ], and brain [ 28 ], have been linked to different disorders in infants and adults, ranging from neurodevelopmental disorders [ 43 ] and psychopathology in preschool children [ 54 ] to brain disorders with onset later in life [ 34 , 39 , 40 , 44 ].…”

“…It is of particular interest in biological psychiatry as a molecular substrate of emotional, neuropsychiatric, and neurodegenerative disorders [ 24 , 25 ] and an important target for psychotropic drugs [ 26 , 27 ]. In addition, HTR2A has been implicated in the pathophysiology of cardiovascular disorders [ 28 , 29 ], diabetes [ 30 ], and obesity [ 31 ].…”

Cardiovascular serotonergic system: Evolution, receptors, transporter, and function

“…A recent study indicates that an A/G polymorphism (rs25531) in individuals with the ll genotype might be associated with a lower risk of ischemic stroke as compared with other SERT genotypes with the same SNP (Mortensen et al, 2018). In the past 20 plus years numerous genetic variations have been detected in most, if not all serotonin receptors, and associated serotonergic elements (Baou et al, 2016; Choi et al, 2020; Gruber et al, 2020; Hoyer, 2020; Jonnakuty & Gragnoli, 2008; Xiang et al, 2019). This is a relatively young field of study with much work yet to be done.…”

Serotonin Receptors and Acetylcholinesterase Gene Expression Alternations: The Potential Value on Tumor Microenvironment of Gastric Cancer

“…Serotonin also affects the production and release of cytokines and cell activation/proliferation. Through the 5-HTR2A receptor, serotonin hinders tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) production [18, 19]. Oncogenic or tumor-suppressive effects of these factors depend on the level of their production, the microenvironment, the type of producing cells, the stage of cancer, and the anti-cancer treatments used [20, 21].…”