Zhang Fuquan, Liu Chenxing, Chen Yaguang, Wang Lifang, Lu Tianlan, Yan Hao, Ruan Yanyan, Yue Weihua, Zhang Dai
Institute of Mental Health, Peking University, Beijing, P.R. China.
Genet Test Mol Biomarkers. 2012 Sep;16(9):1138-41. doi: 10.1089/gtmb.2012.0061.
Genetics play a major role in the etiology of schizophrenia (SZ). Catechol-O-methyltransferase (COMT) is one of the promising candidate genes for SZ. A nonsynonymous single-nucleotide polymorphism (SNP), rs4680, causing a Valine (Val) to Methionine (Met) substitution, has been widely studied in relation to psychiatric phenotypes, including SZ, but with conflicting results. We conducted a two-stage study to examine the association of COMT polymorphisms with SZ in the Han Chinese population.
Association analysis of nine SNPs in 768 patients and 1348 controls failed to detect any positive markers or haplotypes. Then, we tested rs4680 in a validation sample of 963 patients and 992 controls, and no significant association was observed, but the cases significantly deviated from Hardy-Weinberg equilibrium (p=5.7e-4). There was no association of rs4680 with SZ in the combined sample (n=4071, p=0.110, odds ratio=1.08).
Our results do not support the association of COMT with SZ in the Han Chinese population.
遗传学在精神分裂症（SZ）的病因学中起主要作用。儿茶酚-O-甲基转移酶（COMT）是SZ颇具前景的候选基因之一。一种导致缬氨酸（Val）替换为甲硫氨酸（Met）的非同义单核苷酸多态性（SNP），即rs4680，已针对包括SZ在内的精神疾病表型进行了广泛研究，但结果相互矛盾。我们开展了一项两阶段研究，以检验COMT基因多态性与汉族人群中SZ的关联性。
对768例患者和1348例对照中的9个SNP进行关联分析，未检测到任何阳性标记或单倍型。随后，我们在963例患者和992例对照的验证样本中检测rs4680，未观察到显著关联，但病例显著偏离哈迪-温伯格平衡（p = 5.7e - 4）。在合并样本（n = 4071，p = 0.110，优势比 = 1.08）中，rs4680与SZ无关联。
我们的结果不支持COMT与汉族人群中SZ的关联性。
