Department of Anesthesiology, SVIMS University, Tirupati, Andhra Pradesh, 517507, India.
Department of Biotechnology, SVIMS University, Tirupati, Andhra Pradesh, India.
Gen Thorac Cardiovasc Surg. 2020 Oct;68(10):1101-1112. doi: 10.1007/s11748-020-01321-6. Epub 2020 Feb 25.
Catechol-O-methyl transferase (COMT), a catechol-dependent enzyme, plays pivotal role in the development of pain. In different ethnic populations, it is associated with chronic persistent surgical pain (CPSP). In this context, the present study is aimed to assess involvement of COMT allele (Val158Met) in the development of CPSP.
The patients (n = 216) underwent cardiac surgery with median sternotomy were selected to assess the magnitude of the CPSP evaluated with pain questionnaires' after 3 months from surgery. The exon 4 of COMT gene was PCR amplified and sequenced. The quantitative gene expression of COMT using RT-PCR corroborated the COMT enzyme activity.
Among 216 patients who underwent sternotomy procedure, 54 patients showed CPSP even after 3 months from surgery. The sequence analysis revealed that, in 25% (54/216) patients having following one or more alleles: c.472G>A (Val158Met) (reported), and novel c.382C>G;c.383G>C (Arg128Ala), c.373C>G (Arg125Gly), c.370G>A (Val124Met), c.359G>C (Gly120Ala), c.349G>A, c.350G>A(Ala117Ser), c.349G>C, c.351C>A (Ala117Pro), c.349G>A (Ala117Thr), c.350G>C (Ala117Gly), and c.405G>C (Ala135Ser) were observed for the first time in Indian population. Distinct CPSP (≥ 4 NRS pain score) was observed in these patients correlating with COMT enzyme activity (7.80 ± 0.92 units/mg) which is 14 times lowered when compared with non-CPSP patient's (n = 162) 110.15 ± 6.41 units/mg. The findings of COMT gene expression using quantitative RT-PCR corroborated the COMT enzyme activity.
The dominant effect of mutant COMT alleles connecting with low enzyme activity resulted in CPSP, warrants COMT genetic analysis prior to surgery was useful to predict the occurrence of CPSP.
儿茶酚-O-甲基转移酶（COMT）是一种儿茶酚依赖性酶，在疼痛的发展中起着关键作用。在不同的种族人群中，它与慢性持续性手术疼痛（CPSP）有关。在这种情况下，本研究旨在评估 COMT 等位基因（Val158Met）在 CPSP 发展中的作用。
选择接受正中胸骨切开术的心脏手术患者（n=216），以评估手术后 3 个月时使用疼痛问卷评估的 CPSP 程度。对 COMT 基因外显子 4 进行 PCR 扩增和测序。使用 RT-PCR 对 COMT 的基因表达进行定量，以验证 COMT 酶活性。
在接受正中切开术的 216 名患者中，有 54 名患者在手术后 3 个月后仍出现 CPSP。序列分析显示，在 25%（54/216）的患者中存在以下一种或多种等位基因：c.472G>A（Val158Met）（报道），以及新的 c.382C>G；c.383G>C（Arg128Ala），c.373C>G（Arg125Gly），c.370G>A（Val124Met），c.359G>C（Gly120Ala），c.349G>A，c.350G>A（Ala117Ser），c.349G>C，c.351C>A（Ala117Pro），c.349G>A（Ala117Thr），c.350G>C（Ala117Gly），和 c.405G>C（Ala135Ser）首次在印度人群中观察到。在这些患者中观察到明显的 CPSP（≥4 NRS 疼痛评分），与 COMT 酶活性相关（7.80±0.92 单位/mg），与非 CPSP 患者（n=162）的 110.15±6.41 单位/mg 相比降低了 14 倍。使用定量 RT-PCR 进行的 COMT 基因表达研究结果与 COMT 酶活性一致。
与低酶活性相关的突变 COMT 等位基因的显性效应导致 CPSP，因此在手术前进行 COMT 基因分析有助于预测 CPSP 的发生。
