上海交通大學(xué)Bio-X中心是于2005年由NHGG(Neuropsychiatric and Human Genetics Group,神經(jīng)精神與人類遺傳學(xué)研究室)和2000年成立的Bio-X生命科學(xué)研究基地經(jīng)過(guò)重組而成,。近期來(lái)自Bio-X中心的研究人員在Prog Neuropsychopharmacol Biol Psychiatry雜志上發(fā)表文章，揭示了在漢族人群中視黃醛脫氫酶1A2（ALDH1A2）基因和精神分裂癥的陽(yáng)性關(guān)聯(lián),。
在精神分裂癥疾病機(jī)制的研究中有研究者提出＂維生素A調(diào)節(jié)異?？赡苁蔷穹至寻Y發(fā)生的重要因素＂假說(shuō),。影響人體內(nèi)維生素A活性形式--視黃酸水平的主要是其合成限速酶視黃醛脫氫酶ALDH1及羥基化降解視黃酸的CYP26。這些酶類和維生素A運(yùn)載蛋白共同影響其發(fā)揮生物學(xué)功能,。維生素A通路中重要基因與精神分裂癥的關(guān)聯(lián)研究,，將為＂維生素A調(diào)節(jié)異常可能是精神分裂癥發(fā)生的重要因素＂假說(shuō)提供重要信息,。
在這篇論文中，研究人員在617個(gè)漢族人中對(duì)ALDH1A1,，ALDH1A2,，ALDH1A3，CYP26A1,，CYP26B1,，CYP26C1和TTR（甲狀腺素轉(zhuǎn)移酶,，一種維生素A轉(zhuǎn)運(yùn)蛋白）這7個(gè)基因與精神分裂癥的關(guān)系進(jìn)行系統(tǒng)的關(guān)聯(lián)分析，從遺傳學(xué)角度考察維生素A調(diào)節(jié)異常與精神分裂癥是否相關(guān),。研究結(jié)果顯示這些基因的單位點(diǎn)等位基因及基因型均未表現(xiàn)出精神分裂癥相關(guān),，而ALDH1A2基因rs4646642-rs4646580單倍型表現(xiàn)出與疾病的顯著關(guān)聯(lián)（p=0.0055）。該項(xiàng)研究是首項(xiàng)系統(tǒng)地對(duì)維生素A代謝通路上關(guān)鍵基因和精神分裂癥進(jìn)行的關(guān)聯(lián)分析,，其結(jié)果為精神分裂癥維生素A調(diào)節(jié)異常假說(shuō)提供可靠的實(shí)驗(yàn)支持,，并為進(jìn)一步了解疾病機(jī)制指出研究方向。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
