Genetic variants of neurotransmitter-related genes and miRNAs in Egyptian autistic patients

Abstract

Autism is a neurodevelopmental disorder with indisputable evidence for a genetic component. This work studied the association of autism with genetic variations in neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2 TaqI A in 53 autistic patients and 30 healthy individuals. The study also analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher in female patients compared to that in controls (OR = 2.25). MAOB G allele frequency was more significantly increased in autistic patients than in controls (P < 0.001 for both males and females). DRD2 A1+ genotype increased autism risk (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype. Plasma MAOB activity was significantly reduced in G than in A allele carrying males. There was no significant difference in patients and maternal plasma MAOA/B activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21 were found among studied patients. This study threw light on some neurotransmitter-related genes suggesting their potential role in Autism pathogenesis that warrants further studies and much consideration.

Figure 1

Genotyping of MAOA/B and DRD2. (a) Different VNTRs of MAOA. M indicates DNA marker (φx174). Lane 1 indicate 5 tandem repeats at 269 bp. Lane 2 indicates 3 and 5 tandem repeats at 209 and 269 bp. Lane 3 indicates 4 tandem repeats at 239. (b) PCR-based RFLP of MAOB. M is DNA marker (φx174). Lanes 1 and 2 indicate AG genotype at 232 and 146 bp (86 bp not shown). Lane 3 indicates AA genotype at 146 bp. Lanes 4 and 5 indicate GG genotype at 232 bp. (c) PCR-based RFLP of DRD2. Lanes 1 and 4 indicate A1A2 genotype at 237, 126, and 111 bp. Lane 2 indicates A2A2 genotype at 126 and 111. Lane 3 indicates A1A1 genotype at 237 bp.

Figure 2

Sequencing chromatogram of miR-21 and miR-431. (a) it shows the absence of A–G mutation downstream the pre-miR-21. ((b), (c), (d), and (e)) they show the absence of rs12883709 G–A upstream the pre-miR-431, rs76090066 C–T and rs12884005 G–A in the sequence of pre-miR-431, rs61993318 C–T, and rs35695758 G–T/C downstream the pre-miR-431.