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

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

doi:10.12688/f1000research.46399.1

Cited by 3 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, it will be necessary to evaluate the intracellular uric acid and its possible cardiometabolic effects in this population. Moreover, according to our findings, we propose to identify the association of genetic variants in genes involved in urate transport such as ABCG2 , SLC17A1 , SLC17A3 , SLC22A1 , and SLC22A12 that could modify the hyperuricemia status and its comorbidities related 47 in SLE patients.…”

Section: Discussionmentioning

confidence: 83%

Nutritional, biochemical, and clinical determinants of hyperuricemia in systemic lupus erythematosus patients: Relationship with clinical and renal disease activity

Campos-López

Meza-Meza

Pesqueda-Cendejas

et al. 2022

Lupus

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease considered as an independent risk factor for mortality by cardiovascular disease. Currently, uric acid is described as a novel biomarker associated with cardiometabolic risk. However, nutritional and serum determinants that influence hyperuricemia development in autoimmune diseases have not been fully elucidated. This study aimed to assess the nutritional, biochemical, and cardiometabolic determinants of hyperuricemia and its relationship with clinical variables in SLE patients. A cross-sectional study was conducted in 167 SLE patients and 195 control subjects (CS). Nutrient intake, anthropometry, biochemical, and cardiometabolic indexes were evaluated. In SLE patients, adequate protein (OR = 0.4; p = 0.04) and carbohydrate (OR = 0.2; p = 0.01) intakes were associated with a lower risk of hyperuricemia. SLE patients with hyperuricemia presented a higher risk of clinical (OR = 2.2; p = 0.03) and renal activity (OR = 3.4; p < 0.01), as well as triglycerides ≥150 mg/dL (OR = 3.6; p < 0.01), hs-CRP ≥1 mg/L (OR = 3.1; p < 0.01), Kannel score ≥3 (OR = 2.5; p = 0.02), and BMI ≥25 kg/m2 (OR = 2.2; p = 0.02). Oppositely, serum levels of HDL-C ≥40 mg/dL (OR = 0.2; p < 0.01) were associated with a lower risk of hyperuricemia. According to the pharmacotherapy administered, prednisone treatment was associated with a high risk of hyperuricemia (OR = 4.7; p < 0.001). In contrast, the hydroxychloroquine treatment was associated with a lower risk of hyperuricemia (OR = 0.4; p = 0.02). In conclusion, SLE patients with hyperuricemia presented a high risk of clinical and renal activity as well as worse cardiometabolic status. Notably, an adequate intake of protein, carbohydrates, healthy HDL-C serum levels, and hydroxychloroquine treatment could be determinants of lower risk of hyperuricemia.

show abstract

Section: Discussionmentioning

confidence: 83%

Nutritional, biochemical, and clinical determinants of hyperuricemia in systemic lupus erythematosus patients: Relationship with clinical and renal disease activity

Campos-López

Meza-Meza

Pesqueda-Cendejas

et al. 2022

Lupus

View full text Add to dashboard Cite

show abstract

Intestinal Hyperuricemia as a Driving Mechanism for CKD

Johnson

2023

American Journal of Kidney Diseases

View full text Add to dashboard Cite

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

Janakiraman,

Sudhan,

Ahmad

et al. 2024

J. Comput. Biophys. Chem.

View full text Add to dashboard Cite

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the conserved regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from -7.95 kcal/mol to -10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, -5.73 kcal/mol to -8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

show abstract

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

Cited by 3 publications

References 43 publications

Nutritional, biochemical, and clinical determinants of hyperuricemia in systemic lupus erythematosus patients: Relationship with clinical and renal disease activity

Nutritional, biochemical, and clinical determinants of hyperuricemia in systemic lupus erythematosus patients: Relationship with clinical and renal disease activity

Intestinal Hyperuricemia as a Driving Mechanism for CKD

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

Contact Info

Product

Resources

About