Departamento de Anstesiología, Instituto de Ciencias Médicas Sri Venkateswara, Tirupati, India.
Departamento de Anstesiología, Instituto de Ciencias Médicas Sri Venkateswara, Tirupati, India.
Rev Esp Anestesiol Reanim (Engl Ed). 2021 Mar;68(3):128-136. doi: 10.1016/j.redar.2020.09.012. Epub 2021 Jan 19.
Mutations in the exon 4 of the COMT gene are associated with chronic persistent surgical pain (CPSP). Especially COMT mutated allele G472A (Val158Met) associated with CPSP patients is reported in different ethnic population. The purpose of this study is to evaluate the prevalence of genetic mutations and structural variations in exon 4 of COMT that can be related to the appearance of CPSP in patients under sternotomy.
One hundred patients with American Society of Anesthesiologists (ASA) physical status grades i, ii and iii, who underwent sternotomy procedures, were selected to assess the development and magnitude of the CPSP evaluated with pain questionaries' at the end of three months after surgery. This was correlated with COMT allele presence. The exon 4 of COMT gene (that contains the G472A allele) was studied. The polymerase chain reaction (PCR) products were sequenced and mutated sequences were deposited in GenBank®. The structural analysis of COMT was performed using ProCheck® and distortions of three-dimensional tertiary structural orientation was evaluated with root-mean-square deviation (RMSD) score.
Genetic analysis carried out through PCR showed 220 bp amplicons. The 25% of patients with CPSP showed a Numeric Rating Scale (NRS) > 4 pain score. The 20% of these patients have known Val158Met mutation, 5% of patients showed novel mutations c.382C>G, c.383G>C, p.(Arg128Ala). The mutations in COMT gene contributed major structural variations in COMT leading to the formation of inactive COMT that correlates with CPSP.
The results of the present study showed that both novel and previously reported mutations in COMT gene has strong association with CPSP.
COMT 基因外显子 4 的突变与慢性持续性手术疼痛（CPSP）有关。特别是 COMT 突变等位基因 G472A（Val158Met）与不同种族人群的 CPSP 患者有关。本研究旨在评估 COMT 外显子 4 中与 CPSP 患者出现相关的基因突变和结构变异的发生率。
选择 100 名 ASA 身体状况 I、II 和 III 级的行胸骨切开术的患者，评估术后 3 个月时使用疼痛问卷评估 CPSP 的发展和程度。这与 COMT 等位基因的存在相关。研究了 COMT 基因的外显子 4（包含 G472A 等位基因）。通过聚合酶链反应（PCR）对 COMT 基因进行测序，并将突变序列提交给 GenBank®。使用 ProCheck®进行 COMT 的结构分析，并通过均方根偏差（RMSD）评分评估三维三级结构取向的扭曲。
通过 PCR 进行的遗传分析显示出 220bp 的扩增子。25%的 CPSP 患者的数字评分量表（NRS）>4 疼痛评分。其中 20%的患者已知存在 Val158Met 突变，5%的患者显示出新的突变 c.382C>G、c.383G>C、p.（Arg128Ala）。COMT 基因的突变导致 COMT 形成无活性形式，从而导致 COMT 发生重大结构变异，这与 CPSP 相关。
本研究结果表明，COMT 基因中的新突变和先前报道的突变与 CPSP 有很强的相关性。
