Correlation of Major Iron Metabolism Related-Genes Single Nucleotide Polymorphisms (SNPs) with Autism Spectrum Disorder (ASD) in Palestinian Patients. رسالة ماجستير

Abstract

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders with genetic and environmental components. ASD diagnosis is currently based only on clinical criteria, which rises the need for early diagnostic genetic markers. As iron plays a crucial role in brain development, neurotransmitter synthesis, neurons myelination and mitochondrial function, we hypothesized that brain iron dysregulation may play a role in ASD development and pathogenesis. The aim of our study was to assess the association of a number of single nucleotide polymorphisms (SNPs) within transferrin receptor 1 (TFRC) rs11915082, solute carrier family 11 member 2 (SLC11A2) rs1048230 and rs224589, solute carrier family 40 member 1 (SLC40A1) rs1439816, and hepcidin antimicrobial peptide gene (HAMP) rs10421768 with ASD risk. The study included 48 Palestinian individuals with ASD and 88 non-ASD controls. Genotypes were determined by RFLP-PCR or Sanger’s sequencing. Our data revealed that the rs11915082 G allele (p=0.008, OR= 2.06, 95% CI=1.19-3.55) and the rs1439816 C allele (p<0.0001, OR=5.13, 95% CI=3.00-8.79) were associated with ASD pathogenesis. At the genotype level, the polymorphisms rs11915082 (p=0.041), rs1439816 (p=0.000), and rs10421768 (p=0.028) showed a significant association with ASD overall phenotype. Our data demonstrate the role of iron dysregulation in ASD development and pathogenesis and indicate that some genetic variations in iron metabolism genes can be applied as genetic markers for early diagnosis of ASD