Interaction between manganese and SLC6A3 genetic polymorphisms in relation to dyslexia

Excessive exposure to manganese is harmful for neurodevelopment, causing intellectual disability, decreased cognitive ability and diminished language quotients. However, little is known about the link between manganese, genetic susceptibility and the risk of dyslexia. We aim to examine the association between manganese exposure and dyslexia and to test whether the SLC6A3 gene would modify this relationship.

A case-control study was conducted among 239 dyslexic children and 230 controls in China. Urinary manganese concentrations were assessed by inductively coupled plasma mass spectrometry (ICP-MS). Two single nucleotide polymorphisms (rs2975226 and rs27072) in the SLC6A3 gene were selected.

The rs2975226 polymorphism was associated with dyslexia within the recessive model (OR = 1.74, 95 % CI = 1.06-2.86) and the additive model (OR = 1.69, 95 % CI = 1.10-2.61) after multivariate adjustment. Modification effects on the relationship of manganese levels in urine with the risk of dyslexia were suggested in rs27072 (P-value for interaction = 0.003). Furthermore, the highest quartile of urinary manganese was found to have a 3.87-fold (95 % CI = 1.39-10.74) elevated dyslexia risk compared with the lowest quartile among the rs27072 mutation carriers.

The rs2975226 polymorphism was associated with dyslexia and manganese exposure could interact with the rs27072 mutation to increase the risk of dyslexia.