GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations
GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations
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DOI：
10.1042/bst0371415
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发表时间：
2009-12-01
影响因子：
3.9
通讯作者：
Xue, Hong
中科院分区：
文献类型：
--
作者：
Chen, Jianhuan;Tsang, Shui-Ying;Xue, Hong
SCZ（精神分裂症）相关GABA（A）受体（γ-氨基丁酸A型受体）2亚基基因GABRB 2最近与BPD（双相情感障碍）相关。尽管GABRb 2与SCZ的相关性较弱，但在德国人和中国人中均发现了GABRb 2与BPD的显著相关性，尤其是单倍型rs 1816071-rs 187269和rs 1816072-rs 187269，其中M-M变异在疾病中的频率高于对照。BPD显示GABRB 2表达的显著基因型依赖性降低，但程度低于SCZ。观察对GABR 62表达的时间效应。此外，对于rs 18116071、rs 1816072和rs 187269的纯合主要基因型，CON中的表达随时间增加，但SCZ和BPD中的表达随时间减少。这三个SNP（单核苷酸多态性）的基因型进一步与SCZ队列中抗精神病药物剂量相关。这些发现突出了GABR 62在神经精神疾病病因学中的重要性，关于单倍型关联，以及SCZ和BPD中基因表达的减少和时间效应，但在后者中程度较小，支持功能性精神病可以被概念化为连续谱的临床表型而不是不同的类别。
The SCZ (schizophrenia)-associated GABA(A) receptor (gamma-aminobutyric acid type A receptor) 2 subunit gene GABRB2 was recently associated with BPD (bipolar disorder). Although weaker than its association with SCZ, significant association of GABRb2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071-rs187269 and rs1816072-rs187269 for which the M-M variants showed higher frequency in disease than the control. Significant genotype-dependent reduction in GABRB2 expression was shown for BPD, but to a lesser extent than that for SCZ. Temporal effects on GABR62 expression were observed. Moreover, for the homozygous major genotypes of rs18116071, rs1816072 and rs187269, expression increased with time in CON but decreased in SCZ and BPD. The genotypes of these three SNPs (single nucleotide polymorphisms) were further correlated with antipsychotics dosage in SCZ cohorts. The findings highlight the importance of GABR62 in neuropsychiatric disease aetiology, with respect to haplotype association, as well as reduction of and temporal effects on gene expression in both SCZ and BPD, but to a lesser extent in the latter, supporting the suggestion that functional psychosis can be conceptualized as a continuous spectrum of clinical phenotypes rather than as distinct categories.