Genetic Variants and Haplotypes of Tryptophan Hydroxylase 2 and Reelin Genes May Be Linked with Attention Deficit Hyperactivity Disorder in Egyptian Children

Abstract

Attention-deficit hyperactivity disorder (ADHD) has been proposed to stem from multiple etiologies, perhaps genetic in nature with biological and psychosocial motivates. Tryptophan hydroxylase 2 (TPH2) and Reelin (RELN) genes may play a key role in triggering ADHD. The purpose of this case-controlled study was to explore the linkage of the genetic variants of TPH2 and RELN genes with ADHD. One hundred Egyptian children with ADHD and 105 age and sex matched controls constituted the study samples. Genotyping was performed for TPH2 (rs11179027; rs1843809) and RELN (rs736707; rs362691) gene polymorphisms using real time PCR assay. The alleles and genotype frequencies of TPH2 and RELN gene polymorphisms were assessed in all study participants. The frequencies of the alleles of TPH2 rs11179027 (OR = 1.75, 95% CI = 1.08–2.85, p = 0.022), TPH2 rs1843809 (OR = 3.67, 95% CI = 1.82–7.43, p = <0.001), and RELN rs736707 (OR = 1.61, 95% CI = 1.03–2.51, p = 0.035) were significantly associated with ADHD, while there was no significant difference between ADHD patients and controls regarding the frequency of RELN rs362691 (OR = 1.34, 95% CI = 0.73–2.48, p = 0.34). The frequencies of CTAG, CTGG, CTAC, CTGC, and GTAC haplotypes were significantly higher in ADHD patients than in controls (p = 0.011, 0.005, 0.015, 0.001, and 0.027, respectively). In conclusion, TPH2 rs11179027, TPH2 rs1843809, and RELN rs736707 gene alleles and haplotypes might be significantly correlated with the genetic susceptibility to ADHD in Egyptian children.

Attention-deficit/hyperactive disorder updates

“…In addition, TPH2-rs4570625 and TPH2-rs11178997 were reported as risk alleles in a family study ( Walitza et al, 2005 ), but another study performed by Shim et al could not replicate the former ( Shim et al, 2010 ). TPH2 rs11179027 and TPH2 rs1843809 alleles are linked with the genetic predisposition to ADHD in Egyptian children ( Abo El Fotoh et al, 2020 ). The T allele (rs1843809), A allele (rs1386493), and G allele (rs1007023) have been associated with ADHD in the United Kingdom population ( Brookes et al, 2006 ).…”

The effects of tryptophan loading on Attention Deficit Hyperactivity in adults: A remote double blind randomised controlled trial

“…It is also possible that no differences were seen in the current study because there was no deficiency in TRP, or 5-HT in the sample. Previous work has linked changes in the TRP2 genes to ADHD [ 37 , 38 ] but in large UK samples and European samples this link was not found [ 92 , 93 ]. Additionally, dietary data indicates that those with ADHD can have normal levels of dietary TRP, meaning that there may not be a deficiency that can be reversed with TRP loading [ 35 ].…”

“…In support of this, there is evidence that administration of exogenous TRP results in a rise in brain TRP and 5-HT synthesis within the brain [32], which in turn has been shown to result in increased PLOS ONE release of 5-HT in various areas of the brain [33]. Research to date has indicated that lower levels of TRP may be associated with ADHD, at least in adults [34][35][36] and the gene responsible for encoding tryptophan hydroxylase 2 (TPH2), critical for synthesis of central serotonin, has been linked to ADHD symptoms [37,38] as well as performance on standardised laboratory tests of attention [39]. Moreover, tryptophan transport mechanisms have also been found to be altered in ADHD, which could result in lower 5-HT levels [40].…”

Reelin Signaling and Synaptic Plasticity in Schizophrenia

“…It has been demonstrated that disturbances in fear-learning systems may be a common gateway to the development of basic mental disorders [63][64][65]. Both the reelin and tryptophan-kynurenine pathways can be genetically linked and negatively correlated [66].…”