Polymorphism in Variable Number of Tandem Repeats of Dopamine D4 Gene is a Genetic Risk Factor in Attention Deficit Hyperactive Egyptian Children: Pilot Study

Abstract

INTRODUCTIONThe variable number of tandem repeats (VNTR) of the dopamine receptor D4 (DRD4) gene among humans may elucidate individual differences in susceptibility to neuropsychiatric diseases. Dopamine dysfunction may be involved with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. In this study, we report the association between the phenotype of ADHD, a condition characterized by inattentiveness, hyperactivity, and impulsiveness, and a 48-base pair VNTR in exon 3 of the DRD4 polymorphism.SUBJECTS AND METHODSWe used a case control approach conducted on 29 ADHD and 31 ethnically matched control Egyptian children (ages 6–12 years). Cases were assessed by a psychiatric semi-structured interview and the Conners’ Parent Rating Scale. VNTR polymorphisms of the DRD4 gene were done by touchdown PCR program using exon 3-specific primers followed by agarose gel electrophoresis.RESULTSWe observed a significant association between the existence of D4.4 allele of DRD4 and ADHD (P, 0.002); 6.9% of cases showed a single D4.4 and 10.3% showed a double D4.4 as compared to controls in whom D4.4 has never been detected.CONCLUSIONChildren with smaller number of repeat alleles (two to four repeats) of the DRD4 gene have higher possibility to develop ADHD in Egyptian children.

DRD4 Gene Polymorphisms as a Risk Factor for Children with Attention Deficit Hyperactivity Disorder in Iranian Population

“…As it is seen, 4R is more prevalent in Asians than White Caucasians and Europeans [ 14 ]. High prevalence of 4R reported by Shahin et al in Egypt [ 25 ], as well as our study confirms this finding.…”

“…Though these studies were in line with the present study considering 4R as an indicator of ADHD, studies on other populations, specifically White Europeans and Americans showed a greater role of 7R alleles in the development of ADHD [ 25 ]. In contrast, our study did not show any significant relationship between 7R alleles and ADHD.…”

Attention-deficit/hyperactive disorder updates

“…The variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene has been implicated in the etiology of ADHD ( Chang et al, 1996 ; Bidwell et al, 2011 ). Interestingly, different populations have different risk alleles, for instance, the 2-repeat allele (2R) has been noticed in the Han Chinese ( Chang et al, 1996 ) and Koreans ( Hong et al, 2018 ), 4-repeat allele (4R) for Asians while 7-repeat allele (7R) for white Europeans and Americans ( Faraone et al, 1999 ; Hawi et al, 2000 ; Shahin et al, 2015 ; Tabatabaei et al, 2017 ). A haplotype of markers: allele 2 of the 120 bp duplication, 616 C/G substitutions, and 521 C/T substitutions of the C allele can confer a predisposition to ADHD ( Mill et al, 2003 ).…”

Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese

“…As shown in table 1 (model a), a significant association was observed between the DRD4 exon III VNTR and political attitude (OR ¼ 0.820, p ¼ 0.027), the 4R/4R carriers were less liberal than other subjects. Comparison of 4R/4R with all other DRD4 genotypes is not an uncommon practice [68][69][70][71][72][73]. Additionally, presence of a single 7R trumps the effect of the 4R in many studies hence it is not surprising that the 4R/4R grouping has special significance.…”