SNP-SNP interactions within catechol-O-methyltransferase (COMT) gene influence sleep quality in subjects having chronic musculoskeletal pain-A Genetic Exploration ofMusculoskeletal Pain Study (GEMPS).

Objective: To investigate the role and relevance of genetic variants within catechol-o-methyltransferase (COMT) gene as the genetic determinant of sleep quality in musculoskeletal pain, which remains to be examined in the population of Punjab, India. Methods: The present cross sectional study included 493 subjects within age range of 35-65 years from tertiary health care hospitals of Punjab. Musculoskeletal disorders and associated chronic pain was assessed by Nordic Pain Questionnaire (NPQ) and Numerical rating Scale (NRS). Sleep quality was examined using Pittsburgh Sleep Quality Index (PSQI). Contribution of four relevant COMT single nucleotide polymorphisms (SNPs): rs4680 (exon4, A/G), rs4633 (exon3, C/T), rs4818 (exon4, C/G) and rs6269 (exon3, A/G) to sleep quality was investigated by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results:Individually, SNPs rs4680 and rs4633 influenced sleep quality dominantly in the subjects having musculoskeletal pain (P < 0.05). In pair wise SNP-SNP interactive analysis, both these SNPs (rs4680 & rs4633) interacted to affect sleep in dominant x dominant mode. Whereas, SNP rs4680 paired up with rs4818 in additive x dominant mode, rs4633 interacted with rs4680 and rs6269 in interactive mode and rs4818 in concert with rs6269 in additive x additive mode. Conclusion: The present study revealed that SNPs with in COMT gene collaborate and contribute to effect sleep quality in the subjects having musculoskeletal pain. G allele of rs4680 is the main culprit where it shows an epistatic effect on other three SNPs. Nonetheless, their effects are variable depending upon several factors which when revealed will surely comprise one important culprit and that being is COMT gene activity.