Autistic traits and components of the folate metabolic system: an explorative analysis in the eastern Indian ASD subjects

ABSTRACT

Objectives: Proper metabolism of the folate is crucial for maintaining DNA integrity, chromosome structure, methylation, as well as gene expression, and thus, folate is speculated to contribute to the etiology of different disorders. Since the etiology of autism spectrum disorder (ASD) is believed to be influenced by both genetic and environmental factors, we hypothesized that functional single nucleotide polymorphisms (SNPs) affecting folate metabolic pathway may have a causal role in the etiology of ASD.

Methods: We analyzed three SNPs, rs2071010, rs2298444 and rs1801198 (in the folate receptor 1, folate receptor 2 and transcobalamin 2, respectively), in 867 ethnically matched subjects including 206 ASD probands and 286 controls. Plasma vitamin B₆ and folate were measured in age-matched probands and controls.

Results: ASD probands showed a higher frequency of rs2298444 ‘A’ allele (P = 0.01) and genotypes with ‘A’ allele (P = 0.03) when compared with the controls. rs1801198 ‘C’ allele and ‘CG’ genotype also showed higher occurrence in the probands (P = 0.009 and 0.005, respectively). Gender-based stratified analysis revealed a significant higher frequency of rs2298444 ‘A’ allele (P = 0.003), genotypes with rs2298444 ‘A’ allele (P = 0.003) and rs1801198 CG (P = 0.001) in the male probands. Studied variants also showed statistically significant associations with ASD-associated traits measured by the Childhood Autism Rating Scale. ASD subjects exhibited gross deficiency in vitamin B₆ level when compared with age-matched controls (P < 0.001), which correlated with risk genetic variants.

Discussion: We infer from this pioneering study on eastern Indian subjects that vitamin B₆ deficiency, along with risk gene variants, may affect ASD-associated symptoms, warranting further investigation in large cohorts.

KEYWORDS:

• ASD
• CARS score
• folate
• vitamin B₆
• vitamin B₁₂
• folate receptors
• transcobalamin
• rs2298444

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors thankfully acknowledge the Indian Council of Medical Research, Govt. of India for financial support to KM and UR through grant number [GIA/37/DHR-2014]; SS and TS were recruited under the project.