Serotonin risk factors for the development of hypertension in pregnancy

Rudman, Senka Sabolović; Mustapić, Maja; Košec, Vesna; Pivac, Nela; Rudman, Franjo; Mück‐Šeler, Dorotea

doi:10.1007/s00404-014-3461-8

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…As the 5-HT 2A receptor is a key regulator of placentation (influencing placental growth and function), it is suggested to play a role in the pathophysiology of pre-eclampsia [293,294], thereby influencing the maternal immune system activity. However, the association between pre-eclampsia and 5-HT 2A receptor function was not supported in another study [295]. Moreover, it is hypothesized that factors including maternal diet and genetics can influence the 5-HT 2A receptor promoter [296].…”

Section: Synergistic Impact On 5-ht-ergic Systems and Fetal Neurodevementioning

confidence: 87%

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Hanswijk

Spoelder

Shan

et al. 2020

IJMS

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Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.

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Section: Synergistic Impact On 5-ht-ergic Systems and Fetal Neurodevementioning

confidence: 87%

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Hanswijk

Spoelder

Shan

et al. 2020

IJMS

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“…Although genetic associations of SERT were not assessed in that study, their findings point to the fact that regardless of the genotype presented by the mother, plasma 5-HT levels did not show a significant value (p < 0.05) in patients with established PE. In another study carried out by Sabolovic et al in Croatia, platelet 5-HT concentrations were analyzed in pregnant women with PE, in patients with gestational hypertension without proteinuria, and in healthy pregnancies without complications (i.e., controls) [45]; their findings showed that compared with controls, there was a low platelet 5-HT level in PE-and pregnancy-induced hypertension, but unlike us, they did not find differences in the proportions of genotypes of 5-HTTLPR (tri-allelic version) between study groups. Actually, we are not aware of any study evaluating the association between the 5-HTTLPR variant of the SLC6A4 gene and PE and reporting that the S/S genotype decreases the probability of PE.…”

Section: Discussionmentioning

confidence: 99%

“…5-HT transport is performed by the 5-HTT, which regulates intracellular (in neurons and platelets) and extracellular (in synaptic cleft and plasma) 5-HT concentrations, namely, 5-HT function [45]. Several genetic variants of the 5-HTT-linked promoter region (5-HTTLPR) have been identified [46].…”

Section: Introductionmentioning

confidence: 99%

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia

Ramírez-Armas,

Garza-Veloz,

Olivas-Chávez

et al. 2023

JPM

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Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22–0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17–0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

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“…Among the physiological factors for regulating blood pressure, a neurotransmitter and hormone serotonin (5hydroxytryptamine, 5-HT) were considered. Its precise function in normal or altered blood pressure is unclear, likely because of the complex events of blood 5-HT in vitro [10,11]. The association of serotonin and development of hypertension was investigated by the blood platelets, which served as a primary storage location, and were easily accessible source of serotonin [10].…”

Section: Introductionmentioning

confidence: 99%

“…Its precise function in normal or altered blood pressure is unclear, likely because of the complex events of blood 5-HT in vitro [10,11]. The association of serotonin and development of hypertension was investigated by the blood platelets, which served as a primary storage location, and were easily accessible source of serotonin [10]. Blood platelet serotonin 2A receptor (HTR2A, also known as 5-HTR2A), regulates platelet activation and serotonin release; whereas 5-HTR2A located in vascular smooth muscle, endothelial cells, and cardiomyocytes regulate blood pressure and heart rate [12].…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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Serotonin risk factors for the development of hypertension in pregnancy

Cited by 11 publications

References 30 publications

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia

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

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