Effect of gene-environment interaction (arsenic exposure - PON1 Q192R polymorphism) on cardiovascular disease biomarkers in Mexican population

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Highlights

  • Urinary arsenic levels ranged from 5.50 μg/g creatinine to 145 μg/g creatinine.

  • The allele frequency was 0.38 and 0.62 for the 192Q- and 192R-allele, respectively.

  • Strong associations were detected between arsenic exposure biomarker and assessed CVDs biomarkers.

  • The data found in this investigation are exciting and deserve interest of the health Mexican authorities.

Abstract

Cardiovascular diseases (CVDs) are the primary cause of death worldwide. However, little is known about how the interaction between risk factors affects CVDs. Therefore, the aim of this study was to evaluate the effect of the gene-environment interaction (arsenic exposure x PON1 Q192R polymorphism) on serum levels of CVDs biomarkers in Mexican women. Urinary arsenic levels (UAs) ranged from 5.50–145 μg/g creatinine. The allele frequency was 0.38 and 0.62 for the Q and R alleles, respectively. Moreover, significant associations (p<0.05) were detected between UAs and CVDs biomarkers (ADMA, FABP4, and miR-155). Comparable data were found when CVDs biomarkers were evaluated through PON1 genotype, significant (p<0.05) higher serum concentrations of CVDs biomarkers were identified in R allele carriers compared to levels found in Q allele carriers. Besides, a gene-environment interaction was documented. The results of this study we believe should be of significant interest to regulatory authorities worldwide.

Introduction

Worldwide, non-communicable diseases (NCDs) are responsible for approximately 70 % of deaths (∼41 million) annually worldwide (WHO, 2014). Significantly, nearly 85 % of NCD deaths occur in low-and middle-income countries, as México (WHO, 2014). The costs of NCDs treatment are sufficiently large to retard economic and social development, which demands that this issue be addressed and resolved as rapidly as possible (WHO, 2014). Among different NCDs (cardiovascular diseases, diabetes, cancer, and, chronic respiratory diseases), cardiovascular diseases (CVDs) have arisen as the principal cause of death and disability, as approximately 17.9 million deaths each year are attributable to CVDs (WHO, 2014). It has been demonstrated that NCDs (including CVDs) are the consequence of a mixture of different risk determinants such as genetic, physiological, behaviors, as well as environmental factors (WHO, 2014). However, little is known about how the interplay of these factors affects disease risk.

To pursue this issue, gene-environment interaction (G × E) studies are aimed to identify the interplay between risk factors and disease outcomes, particularly with respect to specific population and individual traits (Kolber and Kruger, 2019; Moore, 2018; Picardi et al., 2020). The understanding of G × E interactions is essential for the recognition of susceptible populations and consequently for the development of public health programs to disease risk reduction (Kolber and Kruger, 2019; Moore, 2018; Picardi et al., 2020). Recently, our research group has demonstrated a strong association between arsenic exposure via drinking water and an increased risk of CVDs in exposed Mexican individuals (Ochoa-Martínez et al., 2019; Perez-Vazquez et al., 2017). Also, we have documented an incremented CVDs risk in R allele carriers of the paraoxonase 1 (PON1) rs622 polymorphism (also identified as Q192R) compared to Q allele carriers (Ochoa-Martínez et al., 2020, 2017); indeed, the R allele has been related with the development of CVDs in other recent reports (Gonzalez et al., 2019; Murillo-Gonzalez et al., 2020). Our current focus is the exploration of how a specific genetic susceptibility (PON1 Q192R polymorphism) found in Mexican individuals affects the CDVs risk induced by the exposure to arsenic via drinking water.

Recently, new prognostic biomarkers have been developed with high specificity and sensitivity for evaluating the risk of CVDs (Manson and Bassuk, 2015; Wang et al., 2017). Predictive biomarkers such as asymmetric dimethylarginine (ADMA), fatty acid-binding protein 4 (FABP4), micro-RNAs (miRNAs), among others have successfully been used in large-epidemiological prospective studies to detect individuals at high risk of CVDs development (Furuhashi et al., 2014; Liu et al., 2018; Schulte et al., 2017). Although the use of these CVDs biomarkers has been validated in a broad range of populations, their use as prognostic biomarkers in populations exposed to environmental chemical compounds has been limited. Consequently, supplementary investigations are required to verify the utility of molecules proposed as biomarkers of environmentally mediated CVDs.

Therefore, this study aimed to evaluate the effect of the GxE interaction (arsenic exposure x PON1 Q192R polymorphism) on serum levels of documented prognostic CVDs biomarkers in Mexican women.

Section snippets

Population

The recruitment of enrolled women (n = 185) was completed between June 2018 to February 2019. Assessed sites were selected according to previous investigations that evaluated arsenic levels in drinking water and found concentrations higher than 10 μg/L (Cardenas-Gonzalez et al., 2016; Rocha-Amador et al., 2007, 2011; Rosas-Castor et al., 2014; Ruiz-Huerta et al., 2017). First, an meeting took place involving all eligible individuals (all women living in the assessed sites attended) to explain

Sociodemographic characteristics

Table 1 shows the general characteristics of enrolled women, mean age of 42.5 years (range: 19.0−65.0 years) was identified. The mean weight and height values were 69.0 Kg and 147 cm, respectively. Approximately 60 % of included individuals in the study had a waist circumference higher than the Mexican guideline of 80 cm (Ensanut, 2012). Besides, after BMI was estimated, nearly 65 % of assessed women were overweight and obese. In this regard, in 2012, the National Health and Nutrition Survey

Conclusion

In this study, an interplay between environmental (arsenic exposure) and genetic (PON1 (Q192R) polymorphism) factors on serum CVDs biomarkers levels was detected in people living in Mexico. The detection of G × E interactions is an important tool (as both factors contribute to vulnerability to different diseases, including CVDs) to identify high-risk populations susceptible to develop diseases. To this end, precise recognition of high-risk individuals will facilitate the development of specific

Conflict of Interest

The authors declare no conflict of interest.

CRediT authorship contribution statement

Ángeles C. Ochoa-Martínez: Investigation, Methodology. Yesenia Araiza-Gamboa: Investigation, Methodology. José A. Varela-Silva: Funding acquisition. Sandra T. Orta-García: Investigation, Methodology. Leticia Carrizales-Yáñez: Investigation, Methodology. Iván N. Pérez-Maldonado: Conceptualization, Project administration, Writing - original draft, Writing - review & editing.

Acknowledgements

This work was financed by a grant from: Programa Para el Desarrollo Profesional Docente (PRODEP), Secretaria de Educación Pública (SEP). Apoyo a la reincorporación de ex-becarios 2018. No. De proyecto; UAZ-EXB-400, 511-6/2019.-1007.

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