上海交通大学Bio-X中心是于2005年由NHGG(Neuropsychiatric and Human Genetics Group,神经精神与人类遗传学研究室)和2000年成立的Bio-X生命科学研究基地经过重组而成。近期来自Bio-X中心的研究人员在Prog Neuropsychopharmacol Biol Psychiatry杂志上发表文章，揭示了在汉族人群中视黄醛脱氢酶1A2（ALDH1A2）基因和精神分裂症的阳性关联。
在精神分裂症疾病机制的研究中有研究者提出＂维生素A调节异常可能是精神分裂症发生的重要因素＂假说。影响人体内维生素A活性形式--视黄酸水平的主要是其合成限速酶视黄醛脱氢酶ALDH1及羟基化降解视黄酸的CYP26。这些酶类和维生素A运载蛋白共同影响其发挥生物学功能。维生素A通路中重要基因与精神分裂症的关联研究，将为＂维生素A调节异常可能是精神分裂症发生的重要因素＂假说提供重要信息。
在这篇论文中，研究人员在617个汉族人中对ALDH1A1，ALDH1A2，ALDH1A3，CYP26A1，CYP26B1，CYP26C1和TTR（甲状腺素转移酶，一种维生素A转运蛋白）这7个基因与精神分裂症的关系进行系统的关联分析，从遗传学角度考察维生素A调节异常与精神分裂症是否相关。研究结果显示这些基因的单位点等位基因及基因型均未表现出精神分裂症相关，而ALDH1A2基因rs4646642-rs4646580单倍型表现出与疾病的显著关联（p=0.0055）。该项研究是首项系统地对维生素A代谢通路上关键基因和精神分裂症进行的关联分析，其结果为精神分裂症维生素A调节异常假说提供可靠的实验支持，并为进一步了解疾病机制指出研究方向。（生物谷Bioon.com）
生物谷推荐原始出处：
Progress in Neuro-Psychopharmacology and Biological Psychiatry doi:10.1016/j.pnpbp.2009.08.008
Positive association between ALDH1A2 and schizophrenia in the Chinese population
Chunling Wana, b, , 1, , Yongyong Shia, b, 1, Xinzhi Zhaoa, d, Wei Tanga, b, Ming Zhanga, b, Baohu Jia, b, Hui Zhua, b, Yifeng Xuc, Huafang Lic, Guoyin Fengc and Lin Hea, b, d, ,
aBio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders （Ministry of Education）, Shanghai Jiao Tong University, Shanghai 200030, China
bInstitutes for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
cShanghai Institute of Mental Health, 600 South Wan Ping Road, Shanghai, China
dInstitutes of Biomedical Sciences, Fudan University, 130 Dongan Road, Shanghai 200032, China
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.
