Table 2.

Impact of epigenetic and polymorphic changes by AhR/CYP1 on autism.

Mechanisms	Study Model	Study Design	Gene/Enzyme Changes	Effect on Autism	References
DNA methylation	Human	Autistic subject	↑ DNMT3a, b	↑ DNA damage	[100]
		Autistic men exposed prenatally to PCBs	↑ Methylation of CYP1B1/Cyp1A1	↑ Incidence of autism	[102]
			↓ Methylation of AhRR		[102]
		Newborns with maternal smoking during pregnancy	↑ Methylation of Cyp1A1	↑ Incidence of autism	[103,106]
			↓ Methylation of AhRR	hypomethylation in the early development period can persist for a long period	[103,104,106]
	Rats	Pre- & postnatal exposure to AhR activators	↓ DNA methylation ↓ DNMT1, 3a, 3b mRNA levels in brain	↓ Sp1↓ S-adenosyl methionine levels.	[107,108,109]
			↑ DNMT1 and ↑ ARNT	Delay in onset of puberty in males and affecting estrous cyclicity in females	[111]
	Mice	BTBR T+tf/J mice	↑ DNMT3a, b	↑ DNA damage and autism risk	[100]
Histone modifications	Human	HEK293 cells exposed to PCB Human post-mortem cerebellum autistic individuals	↑ Demethylation of H3K4me3 by Jarid1b ↑ DNMT3a and 3b	↑ Activation of androgen receptor transcriptional activity ↑ DNA oxidative damage genes 8-oxodG → ↑ autism incidence	[100,121]
	Rats	Valproic acid -induced autism in rats	↓ HDAC → hyperacetylation of histone	↑ Neurological birth defect	[115]
	Mice	BTBR T+tf/J mice	↑ DNMT3a and 3b ↔ H3K9ac, H3K56ac, H3K4me3, H3K9me3, H3K27me3, and H4K20me3 compared to the control	↑ DNA oxidative damage genes 8-oxodG → ↑ autism incidence	[100]
MicroRNAs	Mice	Prenatal exposure to TCDD	↑ miR-379	↓ Brain neuronal development → ↑ hypo-social behavior observed	[128]
			↓ let-7	Regulated neuronal stem cell proliferation	[128]
Gene polymorphism	Human	Autistic subjects	↑ ARNT gene (rs2228099), but not AhR rs2066853,	Significant difference in the severity, particularly social communication	[130]
			↑ ARNT2 (rs17225178)	↑ Association with Asperger syndrome	[131]
		Autistic children	CYP1A1 rs1048943 and rs4646422 CYP1A2*1C (rs2069514) CYP1A2*1F (rs762551)	Associated in Thai children and adolescents with autism spectrum disorder	[132]
			↑ CYP1A2*1C (rs2069514), CYP1A2*4 (rs72547516), and CYP1A2*6 (rs28399424) → ↓ CYP1A2 activity → ↑ levels of melatonin	Loss of circadian rhythms and loss of supplemental melatonin effectiveness	[134]