Association Study Between Metallothionein-3 Protein Polymorphisms and Autism
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Genetic susceptibility to high mercury body burden has been suggested as an autism risk factor in children. Metallothionein III (MT3) is the brain-specific form of the metallothionein family, which plays a key role in metal metabolism. We therefore looked for genetic variations in the MT3 gene that might increase the predisposition to autism. DNA was extracted from 132 autistic children and 132 age and gender-matched unrelated controls. All the samples were analyzed for nine single nucleotide polymorphisms (SNPs) with minor allele frequency > 10% in the MT3 gene. The mRNA levels of MT3 in white blood cells were evaluated by real-time PCR. We did not detect any association between these MT3 polymorphisms and the mRNA levels of MT3. We did not detect any association between MT3 polymorphisms and autism risk. However, we detected four novel MT3 SNPs that are not in the human SNP database. The clinical importance of these SNPs needs further investigation. Our data suggest that MT3 gene polymorphisms are not associated with autism.
KeywordsMercury Autism Metallothionein III (MT3) SNP Association study
The authors greatly thank Prof. Lin Jun for her assistance of diagnosis and are grateful to the subjects and their families for participation and collaboration.
This study was supported by the National Natural Science Foundation of China (Grant No: 81,171,669).
Compliance with Ethical Standards
This study was approved by the local Ethics Committees and Hospital Ethics Committee. Written informed consent was obtained from all participating individuals or parents and/or legal guardians.
Conflicts of Interest
The authors declare that they have no conflict of interest.
- Aschner M, Lorscheider FL, Cowan KS, Conklin DR, Vimy MJ, Lash LH (1997) Metallothionein induction in fetal rat brain and neonatal primary astrocyte cultures by in utero exposure to elemental mercury vapor (Hg0). Brain Res 778(1):222–232. https://doi.org/10.1016/S0006-8993(97)01095-0 CrossRefPubMedGoogle Scholar
- Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55(4):611–622. https://doi.org/10.1373/clinchem.2008.112797 CrossRefPubMedGoogle Scholar
- Schultz ST (2010) Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature. Acta Neurobiol Exp (Wars) 70(2):187–195Google Scholar
- Veenstra-Vanderweele J, Christian SL, Cook EH Jr (2004) Autism as a paradigmatic complex genetic disorder. Annu Rev Genomics Hum Genet 5(1):379–405. https://doi.org/10.1146/annurev.genom.5.061903.180050 CrossRefPubMedGoogle Scholar
- Wang Y, Goodrich JM, Gillespie B, Werner R, Basu N, Franzblau A (2012) An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels. Environ Health Perspect 120(4):530–534. https://doi.org/10.1289/ehp.1104079 CrossRefPubMedPubMedCentralGoogle Scholar
- Yoshida M, Watanabe C, Satoh M, Yasutake A, Sawada M, Ohtsuka Y, Akama Y, Tohyama C (2004) Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration. Toxicol Sci 80(1):69–73. https://doi.org/10.1093/toxsci/kfh138 CrossRefPubMedGoogle Scholar
- Yoshida M, Watanabe C, Kishimoto M, Yasutake A, Satoh M, Sawada M, Akama Y (2006) Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vapor. Toxicol Lett 161(3):210–218. https://doi.org/10.1016/j.toxlet.2005.09.007 CrossRefPubMedGoogle Scholar