Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients

PLoS One. 2021 Mar 30;16(3):e0249284. doi: 10.1371/journal.pone.0249284. eCollection 2021.

Abstract

Mental illness is prevalent among hemodialysis (HD) patients. Given that the dopaminergic and serotonergic pathways are involved in the etiology of psychiatric disease, this study evaluated the genetic association of dopamine D4 receptor (DRD4) and serotonin transporter (SLC6A4) genes with psychiatric symptom susceptibility among HD patients. Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depressive symptoms among patients (n = 265). Genetic polymorphisms of DRD4 (48 bp VNTR) and SLC6A4 (5-HTTLPR VNTR and rs25531) were examined using a conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, as appropriate. Significant differences were observed in the distribution of 5-HTTLPR genotypes, SLC6A4 tri-allelic-phased genotype, and DRD4-Exon III VNTR genotypes/alleles between patients with anxiety symptoms versus those with normal/borderline conditions (p<0.05). Binary logistic regression analyses showed that the heterozygous 4,5 VNTR genotype of DRD4 was associated with a higher risk of anxiety symptoms after adjusting for other covariates (odds ratio = 4.25, p = 0.028). None of the studied polymorphisms was linked to depression in HD patients. Collectively, the current findings provide genetic clues to psychopathology in HD patients and suggest that the DRD4 exon III VNTR polymorphism is involved in the etiology of anxiety in this patient population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Exons / genetics*
  • Humans
  • Male
  • Mental Disorders / genetics*
  • Middle Aged
  • Minisatellite Repeats / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Receptors, Dopamine D4 / genetics*
  • Renal Dialysis*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Young Adult

Substances

  • DRD4 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Dopamine D4

Grants and funding

Osama Y. Alshogran has received funding from the Deanship of Scientific Research at Jordan University of Science and Technology (grant number 16/2017). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.