Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children

Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors

“…Range 1 (Mn < 1st quartile): Unadjusted MOR = 0.52, 95% CI: (0.20, 1.38), p = 0.19, p-value for interaction = 0.02; Range 3 vs. Range 1: Adjusted MOR = 0.58, 95% CI: (0.21, 1.58), p = 0.29, p-value for interaction = 0.01) [56]. Similarly, the magnitude and the direction of the association in Pakistani children (Unadjusted MOR = 0.48, 95% CI: (0.15, 1.55), p = 0.22; Adjusted MOR = 0.41, 95% CI: (0.12, 1.40), p = 0.15) was in agreement with the findings from the Jamaican study (Range 2 (1st quartile ≤ Pb < 2nd quartile) vs.…”

“…Using the gWQS method developed, Lee et al reported the association of a mixture of three metals (Pb, Hg, and Mn) with ASD appeared to differ by GSTP1 genotype with a marginally significant interaction effect (p = 0.07) [55]. Furthermore, they found a significant interaction between Mn (categorized into four quartiles) and GSTT1 in relation to ASD (p = 0.02) [56]. In addition, Rahbar et al reported a significant interaction between GSTP1 and ASD status in relation to blood Hg concentrations either in codominant or dominant genetic models for GSTP1 (p < 0.001, p = 0.01, respectively) [57].…”

Genetics and Epigenetics of Manganese Toxicity

“…11 Antioxidant enzyme that scavenges ROS High expression in liver, fat, kidney, and lungs rs769214 ( G /A) Upstream gene variant, eQTL, role in scavenging ROS [ 39 ] 33 to 73 GG ↑ serum Mn AA/AG ↓ serum Mn Risk for spontaneous preterm birth in GG ↑ [ 39 ]/adjusted for sampling time, maternal age, BMI, education, occupation, parity, spontaneous abortion history, folic acid use, medication use, passive smoking, and child gender Glutathione S-transferase theta 1 GSTT1 Chr. 22 Catalyzes the conjugation of reduced glutathione with electrophilic and hydrophilic compounds High expression in liver, brain, duodenum, and prostate (wt/del) 7 Deletion causes loss of function Children with autism spectrum disorder with GSTT1 deletion had increased odds of having higher Mn in blood [ 40 ] Adjusted for socioeconomic status. Range of the GSTT1 deletion frequency in worldwide populations: 11.6 to 51.6% [ 41 ] Apolipoprotein E APOE Chr.…”

“…Further, Rahbar et al [ 40 ] evaluated 266 age- and sex-matched pairs of Jamaican children with autism spectrum disorder and normally developing controls (2–8 years) to determine whether copy number variation of the xenobiotic metabolizing gene glutathione S-transferase theta 1 ( GSTT1 ) modifies the association between blood Mn concentrations and autism spectrum disorder. They found a significant interaction between GSTT1 copy number and blood Mn concentrations: compared to controls, autism spectrum disorder cases with GSTT1 homozygous for deletion of the gene on both chromosomes had 4.35 times higher odds of blood Mn concentrations above 12 μg/l vs. below 8.3 μg/l.…”