Interaction between manganese and SLC6A3 genetic polymorphisms in relation to dyslexia

Area of Science:

• Neurodevelopmental disorders
• Environmental toxicology
• Human genetics

Background:

• Manganese is essential but excessive exposure harms neurodevelopment, leading to cognitive and language deficits.
• The interplay between manganese exposure, genetic factors, and dyslexia risk remains poorly understood.
• The SLC6A3 gene is investigated for its potential role in modifying manganese's impact on dyslexia.

Purpose of the Study:

• To investigate the association between manganese exposure and the risk of dyslexia.
• To determine if the SLC6A3 gene (specifically polymorphisms rs2975226 and rs27072) modifies the relationship between manganese exposure and dyslexia.

Main Methods:

• A case-control study involved 239 children with dyslexia and 230 controls in China.
• Urinary manganese concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS).
• Two single nucleotide polymorphisms (SNPs), rs2975226 and rs27072, within the SLC6A3 gene were genotyped.

Main Results:

• The rs2975226 polymorphism showed a significant association with dyslexia under recessive and additive models.
• A significant interaction (P=0.003) was observed between manganese levels and the rs27072 polymorphism regarding dyslexia risk.
• Individuals with the rs27072 mutation and in the highest quartile of urinary manganese had a 3.87-fold increased risk of dyslexia.

Conclusions:

• The rs2975226 polymorphism is linked to dyslexia.
• Manganese exposure and the rs27072 mutation in the SLC6A3 gene interact to elevate dyslexia risk, suggesting a gene-environment interaction.