Abstract
Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes life-style interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipid-lowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.
Highlights
Metabolic diseases are interrelated disorders that contribute to the development of cardiovascular disease, which have experienced a notable increase in their rates in the last decades due to several contributing factors as ageing and mainly those related to life-style changes which are reflected in high prevalence of obesity, type 2 diabetes (T2D) and, lately, metabolic syndrome (MetS) worldwide;
One study investigated the influence of polymorphisms within the NR1I2, NR1I3, PPARA and RXRA on simvastatin or atorvastatin response in Brazilian HC patients treated during one year
We identified only one study from our research group that evaluated the role of polymorphisms in the genes encoding the tumor necrosis factor alpha (TNF) and interleukin 6 (IL6) in 53 T2D patients treated with pioglitazone, an antidiabetic drug that enhances the expression of the peroxisome proliferator-activated receptor-gamma (PPARγ), leading to improved sensitivity to insulin but that can induce bone loss
Summary
Metabolic diseases are interrelated disorders that contribute to the development of cardiovascular disease, which have experienced a notable increase in their rates in the last decades due to several contributing factors as ageing and mainly those related to life-style changes (unhealthy dietary pattern, physical inactivity and sedentary lifestyle, smoking, among others) which are reflected in high prevalence of obesity, type 2 diabetes (T2D) and, lately, metabolic syndrome (MetS) worldwide;. Several pharmacogenetic studies have been performed in different populations around the world, in order to elucidate the influence of gene polymorphisms on the response to drugs used in the management of hyperglycemia, high blood pressure (BP), dyslipidemia and other metabolic diseases. Several long-term prospective studies have consistently shown that characteristic alterations in lipid profile observed in dyslipidemia, such as hypercholesterolemia and hypertriglyceridemia (isolated or mixed if both are present), as well as low levels of high-density lipoprotein (HDL) cholesterol, have increased incidence of cardiovascular disease (CVD) These alterations in the lipid profile are etiologically classified as primary dyslipidemia, when the cause is of genetic origin; or secondary, if the alteration in the lipid profile is a consequence of inadequate life-style, some morbid conditions or as an adverse reaction to drugs (Faludi et al, 2017).
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