Genetic Susceptibility to Autism Spectrum Disorders: Folate Pathway Polymorphisms, Mediterranean Diet and...

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Nutritional Biochemistry

Background:

• Autism spectrum disorder (ASD) has a complex, multifactorial etiology linked to genetic factors and folate metabolism.
• Genetic variations in folate pathway enzymes like MTHFR and MTRR are implicated in ASD susceptibility.

Purpose of the Study:

• To investigate the association between MTHFR (C677T, A1298C) and MTRR (A66G) gene polymorphisms and ASD risk in an Apulian cohort.
• To analyze genotypic, allelic, and haplotype frequencies in relation to ASD.

Main Methods:

• Genotyping of MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms using Real-time/FRET.
• Analysis of 73 ASD patients and 84 healthy controls from the University Hospital Policlinico, Bari.
• Statistical evaluation of genetic distributions and haplotype frequencies, including in silico protein structure analysis.

Main Results:

• No significant difference in single genotype distributions between ASD cases and controls.
• The MTHFR 677T allele was less frequent in ASD patients (37.67%) than in controls (50%), suggesting a protective effect (p=0.038).
• The MTHFR/MTRR C-C-G haplotype emerged as a significant risk factor for ASD (OR=3.60, p=0.019).
• In silico analysis confirmed MTHFR C677T polymorphism destabilizes protein structure.

Conclusions:

• The MTHFR 677T allele may confer a protective effect against ASD in the studied population.
• A specific MTHFR/MTRR haplotype (C-C-G) is associated with increased ASD susceptibility.
• Evolutionary factors and high folate intake within the Mediterranean diet might influence the MTHFR 677T allele frequency.