Polymorphisms of the genes ABCG2, SLC22A12 and XDH and their relation with hyperuricemia and hypercholesterolemia in Mexican young adults.

Juan Manuel Vargas-Morales,Armando Tovar,Jorge Alejandro Alegría-Torres,Lilia G Noriega,Celia Aradillas-García,Martha Guevara-Cruz

doi:10.12688/f1000research.46399.1

Abstract

Background: Hyperuricemia is a pathological condition associated with risk factors of cardiovascular disease. In this study, three genetic polymorphisms were genotyped as predisposing factors of hyperuricemia. Methods: A total of 860 Mexicans between 18 and 25 years of age were genotyped for the ABCG2 (rs2231142), SLC22A12 (rs476037), and XDH (rs1042039) polymorphisms, as predisposing factors of hyperuricemia. Biochemical parameters were measured by spectrophotometry, while genetic polymorphisms were analyzed by real-time PCR. An analysis of the risk of hyperuricemia in relation to the variables studied was carried out using a logistic regression. Results: Male sex, being overweight or obese, having hypercholesterolemia or having hypertriglyceridemia were factors associated with hyperuricemia ( p ≤ 0.05). The ABCG2 polymorphism was associated with hyperuricemia (OR = 2.43, 95% CI: 1.41-4.17, p = 0.001) and hypercholesterolemia (OR = 4.89, 95% CI: 1.54-15.48, p = 0.003), employing a dominant model, but only in male participants. Conclusions: The ABCG2 (rs2231142) polymorphism increases the risk of hyperuricemia and hypercholesterolemia in young Mexican males.

Highlights

Hyperuricemia is an abnormal metabolic trait defined as serum uric acid levels above 6 and 7 mg/dL for women and men, respectively (Bardin & Richette, 2014), and is associated with other cardiometabolic risk factors such as obesity, diabetes, hypertension, and dyslipidemia (Martínez-Quintana et al, 2016; Zuo et al, 2016)
Medians and genotypic distribution between hyperuricemic and normouricemic participants were analyzed using the MannWhitney U test, finding differences for sex, Body Mass Index (BMI), systolic and diastolic pressure, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) (p =
In this study, we found that the ABCG2 polymorphism increases the risk of hyperuricemia as well as of hypercholesterolemia in young Mexican males

Summary

Introduction

Hyperuricemia is an abnormal metabolic trait defined as serum uric acid levels above 6 and 7 mg/dL for women and men, respectively (Bardin & Richette, 2014), and is associated with other cardiometabolic risk factors such as obesity, diabetes, hypertension, and dyslipidemia (Martínez-Quintana et al, 2016; Zuo et al, 2016). Some genes involved in the metabolism of purines or urates have versions that appear to predispose to a hyperuricemic condition. Some of these are the ABCG2 gene that encodes a membrane transporter, which exports urates to the kidney and intestine (Woodward et al, 2009); and the SLC2A9 gene that encodes a kidney protein called GLUcose Transporter 9 (GLUT9), an important flow regulator of urates in the proximal tubules (Caulfield et al, 2008). Three genetic polymorphisms were genotyped as predisposing factors of hyperuricemia. Methods: A total of 860 Mexicans between 18 and 25 years of age were genotyped for the ABCG2 (rs2231142), SLC22A12 (rs476037), and XDH (rs1042039) polymorphisms, as predisposing factors of hyperuricemia. Conclusions: The ABCG2 (rs2231142) polymorphism increases the risk of hyperuricemia and hypercholesterolemia in young Mexican males

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