Mutations and structural variations in Catechol-O-methyltransferase gene of patients exhibiting chronic persistent...

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.