Doyle Anne E Sullivan, Goodman Julie E, Silber Paul M, Yager James D
Division of Toxicological Sciences, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205-2179, USA.
Cancer Lett. 2004 Oct 28;214(2):189-95. doi: 10.1016/j.canlet.2004.06.033.
A single nucleotide polymorphism in the COMT (catechol-O-methyltransferase) gene that alters the amino acid sequence at codon 108 of S-COMT from val to met (val108met polymorphism) has been associated with a number of diseases and neuropsychiatric disorders. Several studies have shown that the met108 allele (COMTL) is associated with three to four-fold lower levels of COMT activity, compared to the val108 allele (COMTH), in extracts of human erythrocytes, liver and kidney tissue. We hypothesized that the differences in COMT activity observed in these studies were due to differing levels of COMT protein in cells and tissues with varying COMT genotypes. In order to address this, we obtained hepatocytes from 31 Caucasian female donors and determined their COMT genotype, COMT activity and COMT protein levels. We found that both cytosolic COMT activity and cytosolic COMT protein levels are lower in hepatocytes from COMTLL individuals, and that COMT activity levels correlate with COMT protein levels. Therefore, lower COMT activity seen in tissues and cells with the COMTLL genotype is likely due to lower COMT protein levels compared with tissues and cells from COMTHH individuals.
儿茶酚-O-甲基转移酶（COMT）基因中的一个单核苷酸多态性，可使S-COMT第108密码子处的氨基酸序列从缬氨酸变为甲硫氨酸（缬氨酸108甲硫氨酸多态性），这与多种疾病和神经精神障碍有关。多项研究表明，与缬氨酸108等位基因（COMTH）相比，甲硫氨酸108等位基因（COMTL）在人红细胞、肝脏和肾脏组织提取物中的COMT活性水平低三到四倍。我们推测，这些研究中观察到的COMT活性差异是由于不同COMT基因型的细胞和组织中COMT蛋白水平不同所致。为了解决这个问题，我们从31名白种女性供体中获取了肝细胞，并确定了它们的COMT基因型、COMT活性和COMT蛋白水平。我们发现，COMTLL个体的肝细胞中胞质COMT活性和胞质COMT蛋白水平均较低，且COMT活性水平与COMT蛋白水平相关。因此，与COMTHH个体的组织和细胞相比，COMTLL基因型的组织和细胞中COMT活性较低可能是由于COMT蛋白水平较低。
