Association of oxytocin levels and oxytocin receptor gene polymorphism (rs2254298) with cardiovascular risk factors in Brazilian elderly from Primary Health Care
Introduction
The demographic aspects of the Brazilian population's aging rate have been a recent source of concern, due to the increase in the prevalence of non-communicable chronic diseases (DCNT), mainly cardiovascular and metabolic diseases, which negatively impact the quality of life and the daily routine of these individuals (Mazzoccante, Moraes, & Campbell, 2012).
The mortality rate associated to cardiovascular diseases is the result of a series of interrelated risk factors, such as genetics, hormonal and behavioral (Mansur & Favarato, 2012). Within this context, oxytocin, a neuropeptide known as the “love hormone,” has been largely studied due to its relevance to many physiological processes in the body, which include food control and modulation of carbohydrate and lipid metabolism (Blevins et al., 2014; Cai & Purkayastha, 2013).
Oxytocin plays an important role in hemodynamic mechanisms, such as the regulation of blood pressure and the release of atrial natriuretic peptide (Japundžić-Žigon, 2013; Wsol, Kasarello, Kuch, Gala, & Cudnoch-Jedrzejewska, 2016). Furthermore, studies with rodents have shown that oxytocin can reverse insulin resistance and glucose intolerance due to the presence of oxytocin receptors in the islets of Langerhans (Zhang et al., 2013; Klement et al., 2017).
The main effects of oxytocin are mediated by its receptor, which is comprised by nine amino acids coupled to the G protein. In 1994, the oxytocin receptor gene (OXTR) was mapped by Inoue et al. (1994). The OXTR is located in the short arm of human chromosome 3p25 and it consists of three exons and four introns. The single nucleotide polymorphism on OXTR rs2254298 is characterized by the replacement of guanine (G) for adenine (A), which is located in the third intron (Inoue et al., 1994; Mizumoto et al., 1997).
Caucasians usually carry two copies of the G allele, whereas the A allele is quite common in Asian individuals. OXTR polymorphism (rs2254298) has been associated to the onset of anxiety disorders and depression (Brune, 2012; Chelala, Khan, & Lemoine, 2008; Gimpl & Fahrenholz, 2001). Moreover, the variation of this polymorphism has also been associated to overeating and endophenotypic traits, such as the preference for sweet and greasy foods. Davis, Patte, Zai, and Kennedy (2017) suggested an association between OXTR and eating disorders, as they that the A-allele carriers had a greater preoccupation with food consumption and weight. OXTR may be related to appetite and food ingestion that, if correlated with the relatively low serum oxytocin levels, may contribute to the onset of obesity (Davis et al., 2017).
Nevertheless, the influence of the OXTR polymorphism on others cardiovascular risk factors (CVD), such as hypertension, diabetes mellitus (DM), and dyslipidemia, has remained unclear in the literature, as well as the relationship of serum oxytocin with these diseases, especially in the elderly.
This single-nucleotide polymorphism rs2254298 was chosen because there are many studies associating it with depression and rare with cardiovascular risk in the elderly. In addition, our results are part of a larger project investigating this polymorphism with affective and neuropsychiatric disorders.
Therefore, the hypothesis to be answered in this paper suggests that depressed individuals exposed to cardiovascular risk factors may carry the same predisposition or genetic trait, which would be associated to a social or food behaviour. Taking into consideration the ideas above, the objectives of this study were to investigate if there is an association between serum oxytocin concentration and OXTR polymorphism rs2254298 with cardiovascular and metabolic risk factors in a population of elderly individuals treated in Primary Health Care centres in Brazil.
Section snippets
Subjects and study design
This was a non-probabilistic, cross-sectional study which included 177 elderly individuals attending primary health care units in the eastern and north-eastern regions of Porto Alegre, a Brazilian municipality and the capital city of the southernmost state of Brazil - Rio Grande do Sul. The study was part of a Special Visiting Project (PVE), a collaborative network study among the Psychiatry Service of the University of Lausanne-Switzerland, the service of the Institute of Gerontology and
Results
The sample consisted of individuals with an average age of 72.6 ± 6.9 years, being most of them females (n = 129; 72.9%), Caucasian (n = 121; 74.2%), African Brazilian (n = 30; 18.45%), brown (11; 6.7%), and one (0.7%) was Asian Brazilian.
Table 1 lists the general characteristics of the studied population, being the distribution of the genotype frequencies of this population the following: GG = 62 (44.3%), AG = 58 (41.4%) and AA = 20 (14.3%).These frequencies were in Hardy-Weinberg equilibrium
Discussion
The purpose of this study was to verify if there was an association between serum oxytocin levels and OXTR gene polymorphism with cardiovascular and metabolic risk factors in elderly people. The first hypothesis was confirmed, demonstrating a correlation between oxytocin, triglycerides and the nutritional status of the investigated individuals. Indeed it is a pioneering study in aging and cardiogeriatrics areas, and it may be used as a guide for further scientific advances about the
Statement of funding
This doctorate study was supported by a grant from the Coordination of Improvement of Higher Education Personnel (CAPES) - Doctorate Course in Biomedical Gerontology (PUCRS) - and by a Special Visitor Project Proposal (PVE) A031.
Author statement contributors
C.B.J. Participated in the elaboration, construction of the methodological design, clinical evaluation of the study subjects, statistical analysis and discussion of the results. I.G and M.G.V.G designed the study and managed the literature searches and analyses. C.A.B carried out the genotypes and database. L.S.R was responsible for performing the anthropometry. B.L.C was responsible for the analysis of oxytocin and serum cortisol.
All authors contributed to and have approved the final
Acknowledgments
We would like to thank the National Post-Doctoral Program of the Coordination of Improvement of Higher Education Personnel (PNPD/CAPES) and Financial Code 001 for the scholarship. And the Researcher and Psychiatrist Armin von Gunten (Department of psychiatry, University Hospital Lausanne. Lausanne, Switzerland) for suggesting us to investigate the OXTR polymorphism.
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