Effect of DRD4 Receptor -616 C/G Polymorphism on Thalamic GABA Levels in Pediatric Patients With Primary Nocturnal Enuresis

Hongbin Sun; Yi You; Bing Xue; Shanshan Xiao; Yao Lu; Hongwei Ma; Yang Hou; Bing Yu; Xin Pan

doi:10.1002/jmri.27782

Effect of DRD4 Receptor -616 C/G Polymorphism on Thalamic GABA Levels in Pediatric Patients With Primary Nocturnal Enuresis

J Magn Reson Imaging. 2021 Dec;54(6):1857-1864. doi: 10.1002/jmri.27782. Epub 2021 Jun 13.

Authors

Hongbin Sun¹, Yi You², Bing Xue², Shanshan Xiao², Yao Lu³, Hongwei Ma⁴, Yang Hou², Bing Yu², Xin Pan¹

Affiliations

¹ Department of Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
² Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
³ Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China.
⁴ Department of Developmental Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

PMID: 34121249
DOI: 10.1002/jmri.27782

Abstract

Background: The single nucleotide polymorphism (SNP) of dopamine D4 receptor (DRD4) promoter (-616; rs747302) is associated with abnormalities of the thalamus in children suffering from primary nocturnal enuresis (PNE).

Purpose: To investigate the effect of DRD4 -616 C/G SNP on thalamic gamma-aminobutyric acid (GABA) levels in PNE children.

Study type: Prospective, observational.

Subjects: One hundred and seventy-six children with PNE and 161 healthy control children.

Field strength/sequence: 3 T, three-dimensional T1-weighted turbo field echo sequence and MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) MRS sequence.

Assessment: The MEGA-PRESS MRS sequence was used to measure thalamic GABA spectra. The thalamic GABA+ level was calculated using the Gannet 3.0 software package for each participant. A questionnaire was used to determine arousal from sleep (AS) scores.

Statistical tests: Comparisons of the AS scores and thalamic GABA+ levels were performed using the Mann-Whitney U test between C-allele carriers and GG homozygotes in the PNE and control groups. Spearman correlation analysis was performed to determine the association between AS scores and thalamic GABA levels in PNE children.

Results: Thalamic GABA levels in the PNE group were significantly higher than those in the healthy control group (0.178 (0.169-0.186) vs. 0.154 (0.146-0.164), Z = 8.526, P_corrected < 0.001). The GABA levels in C-allele carriers were significantly higher than those in GG homozygotes in both the PNE and control groups (0.184 (0.181-0.193) vs. 0.170 (0.165-0.177), Z = 8.683, P_corrected < 0.001; 0.166 (0.156-0.170) vs. 0.147 (0.141-0.152), Z = 9.445, P_corrected < 0.001). GABA levels in the thalamus were also significantly and positively correlated with AS scores in C-allele carriers in the PNE group (r = 0.747, P < 0.05).

Data conclusion: DRD4 -616 C allele may be associated with increased thalamic GABA+ levels, especially in C-allele carrying PNE children.

Level of evidence: 2 TECHNICAL EFFICACY STAGE: 3.

Keywords: enuresis; magnetic resonance spectroscopy; school children.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Child
Humans
Nocturnal Enuresis* / genetics
Prospective Studies
Receptors, Dopamine D4* / genetics
Thalamus / diagnostic imaging
gamma-Aminobutyric Acid / analysis*

Substances

DRD4 protein, human
Receptors, Dopamine D4
gamma-Aminobutyric Acid