Positive association between ALDH1A2 and schizophrenia in the Chinese population.

Abstract

Vitamin A (retinol), in the biologically active form of retinoic acid (RA), has been proposed as involved in the pathogenesis of schizophrenia. We hypothesized that genetic basis of genes encoding RA metabolism enzymes, which control the cellular RA level, might be associated with this disease. This cascade genetic association model, using markers in genes of synthesis and degradation enzymes within the retinoid cascade, would better fit the biological character of the retinoid hypothesis than the single gene strategy. In the present study we chose to investigate 7 genes involved in the synthesis, degradation and transportation of RA, ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, CYP26B1, CYP26C1 and Transthyretin (TTR), for their roles in the development of schizophrenia. We genotyped 18 single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of these 7 genes using LDR technology in the 617 Chinese Han subjects. Case-control analyses were performed to detect association of these 7 genes with schizophrenia. Association analyses using both allelic and genotypic single-locus tests revealed no significant association between the risk for each of investigated gene and schizophrenia. However, analyses of multiple-locus haplotypes indicated that the overall frequency of rs4646642-rs4646580 of ALDH1A2 gene showed significant difference between patients and control subjects (p=0.0055). We also employed multifactor dimensionality reduction method to detect multilocus effects. In summary, in this work we show multiple candidate genes involved in retinoid cascade in schizophrenics. In addition, our results suggest a positive association between ALDH1A2 and schizophrenics in the Chinese population and support the retinoid hypothesis of schizophrenia.

• Authors: Chunling Wan, Yongyong Shi, Xinzhi Zhao, Wei Tang, Ming Zhang, Baohu Ji, Hui Zhu, Yifeng Xu, Huafang Li, Guoyin Feng, Lin He
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 33 Issue 8 Pg. 1491-5 (Nov 13 2009) ISSN: 1878-4216 [Electronic] England
• PMID: 19703508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehyde Dehydrogenase 1 Family
• ALDH1A2 protein, human
• Retinal Dehydrogenase

Topics

• Adult
• Aldehyde Dehydrogenase 1 Family
• Asian People (genetics)
• Case-Control Studies
• Chi-Square Distribution
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Retinal Dehydrogenase (genetics)
• Schizophrenia (genetics)