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.