scholarly journals The Effects of CYP2A6 Gene Polymorphism on Cardiovascular Diseases

2021 ◽  
Vol 10 (3) ◽  
pp. 217-233
Author(s):  
Preiffer A. Prasojo ◽  
Christine Patramurti
Keyword(s):  
Insulin Resistance ◽  
Nervous System ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Gene Polymorphism ◽  
Blood Levels ◽  
Nicotine Metabolism ◽  
Exclusion Criteria ◽  
Sympathetic Nervous ◽  
Cyp2a6 Gene

The CYP2A6 gene encodes its enzymes and is highly polymorphic, leading to variations in allele forms, both in the active and inactive states. These changes result in a decrease, increase or deletion of enzyme activities. One of the specific substrates is nicotine, an active compound in cigarettes. Nicotine is a major risk factor for cardiovascular diseases, and the inactive alleles tends to decrease its metabolism and expands the threat to infections. Therefore, this study aims to evaluate the effects of CYP2A6gene polymorphism on cardiovascular diseases. Relevant literatures were obtained using PubMed and Google Scholar, while the eventual selection followed the inclusion and exclusion criteria. Based on this review, the CYP2A6 gene polymorphism, both in increased, decreased or deleted alleles, was known to significantly influence nicotine metabolism and its blood levels. Species categorized as slow or poor metabolizers, tend to decrease the nicotine metabolism, but result in greater nicotine blood levels. This outcome subsequently accelerated the activation of the sympathetic nervous system, lipolysis, and insulin resistance, to trigger atherosclerosis. In summary, CYP2A6 gene polymorphism is known to increase cardiovascular diseases, particularly among active or passive smokers.

Hypertension and insulin resistance: role of sympathetic nervous system activity

1992 ◽  
Vol 263 (5) ◽  
pp. E935-E942 ◽  
Author(s):  
M. A. Supiano ◽  
R. V. Hogikyan ◽  
L. A. Morrow ◽  
F. J. Ortiz-Alonso ◽  
W. H. Herman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Multiple Regression Model ◽  
Metabolic Effects ◽  
Plasma Norepinephrine ◽  
Intravenous Glucose ◽  
Arterial Blood ◽  
Sympathetic Nervous ◽  
Intravenous Glucose Tolerance Tests

he purpose of this study was to test the hypothesis that heightened sympathetic nervous system (SNS) activity contributes to the mechanism by which hypertension is associated with insulin resistance in humans. We performed frequently sampled intravenous glucose tolerance tests to determine tissue sensitivity to metabolic effects of insulin (SI) and measured plasma norepinephrine (NE) levels in 21 normotensive and 14 hypertensive Caucasian subjects. Compared with the normotensive subjects, hypertensive subjects had decreased SI (5.4 +/- 0.5 vs. 4.0 +/- 0.7 x 10(-5) x min-1 x pM-1; P = 0.03) but similar plasma NE levels (normotensive: 1.82 +/- 0.12 vs. hypertensive: 1.73 +/- 0.16 nM; P = 0.23). In a multiple regression model, only body mass index (BMI) and mean arterial blood pressure (MABP) were significant independent predictors of SI [SI = (-0.513)(BMI) + (-0.058)(MABP) + 23.6; r = 0.748; P = 0.0001]; age, plasma glucose, epinephrine, and NE level did not enter this model. As an additional test of this hypothesis, seven hypertensive subjects were restudied after 10 days of guanadrel therapy to determine whether SI would increase during suppression of SNS activity by guanadrel. Despite a significant reduction in plasma NE levels with guanadrel (baseline: 1.63 +/- 0.18 vs. guanadrel: 0.99 +/- 0.14 nM; P = 0.01), there was no significant change in SI (baseline: 2.97 +/- 0.78 vs. guanadrel: 2.41 +/- 0.54 x 10(-5).min-1 x pM-1; analysis of variance P = 0.57). We conclude that, in the Caucasian population we studied, heightened SNS activity is not essential for the insulin resistance observed in hypertensive humans.

scholarly journals Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

2007 ◽  
Vol 51 (7) ◽  
pp. 1128-1133 ◽  
Author(s):  
Ivana Pivatto ◽  
Patricia Bustos ◽  
Hugo Amigo ◽  
Ana Maria Acosta ◽  
Antonio Arteaga
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Resistance Index ◽  
Cross Sectional Study ◽  
Blood Levels ◽  
Model Assessment ◽  
Cross Sectional ◽  
Predictive Values ◽  
The Metabolic Syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

scholarly journals Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Paola Canale ◽  
Simone Manca di Villahermosa ◽  
Giuliana Martino ◽  
Valentina Rovella ◽  
Annalisa Noce ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Overactivity ◽  
Area Of Interest ◽  
The Metabolic Syndrome ◽  
Sympathetic Nervous ◽  
Permissive Role

The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.

The sympathetic nervous system and insulin resistance in achilles tendinopathy

2015 ◽  
Vol 19 ◽  
pp. e98
Author(s):  
J. Jewson ◽  
E. Lambert ◽  
M. Storr ◽  
G. Lambert ◽  
J. Gaida
Keyword(s):  
Insulin Resistance ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Achilles Tendinopathy ◽  
Sympathetic Nervous

Mapping of genetic determinants of the sympathoneural response to stress

2005 ◽  
Vol 20 (2) ◽  
pp. 183-187 ◽  
Author(s):  
I. Klimeš ◽  
K. Weston ◽  
D. Gašperíková ◽  
P. Kovács ◽  
R. Kvetňanský ◽  
...  
Keyword(s):  
Nervous System ◽  
Cardiovascular Diseases ◽  
Sympathetic Nervous System ◽  
Adrenal Medulla ◽  
Brown Norway ◽  
System Response ◽  
Genetic Determination ◽  
A Genome ◽  
Response To Stress ◽  
Sympathetic Nervous

Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats ( n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for ∼20% of the total variation in both the early and late NE responses in the F2 rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.

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