engleski

Experimental pain threshold and tolerance analysis points to ROCK2 as a novel gene involved in nociception

Introduction: The aim of this study was to investigate the genetic basis of acute pain. Materials and methods: We measured experimentally-induced mechanical pain threshold (least stimulus intensity) and pain tolerance (maximum tolerance stimulus intensity) in 1, 114 previously genotyped subjects from the 10, 001 Dalmatians cohort. The subjects were genotyped with either HumanHap 300v1 or 370CNV-Quad. QC protocol included removal of individuals with less than 97% genotyping rate, call rate below 98%, minor allele frequency below 2% and P-value for Fisher‘s exact test of Hardy-Weinberg equilibrium below 10E-10. Since subjects originated from three different groups, we performed a fixed effects meta-analysis. Results: The results suggested one marginal hit for pain tolerance on chromosome 2, belonging to ROCK2 gene (rs4260216, P=5.3x10-7). The effect size of this SNP was comparable among all subsets, with similar allele frequencies and with very low heterogeneity (I2=0, P=0.540). This SNP also showed nominal significance association with pain threshold (P=6.8x10-4). There were no other SNPs in this region with suggestive significance, due to very low regional LD patterns. Conclusion: This gene was previously implied in cytokinesis, smooth muscle contraction and focal adhesion, thus suggesting a plausible biological role in nociception, which was also recently implied in mice study. Replication efforts on humans should focus on independent population, larger sample sizes and possibly even patients with chronic pain. Funding: Medical Research Council UK, Croatian Science Foundation grant 8875 and EFIC-EGG grant for young investigators. We gratefully acknowledge contribution from the Institute for Anthropological Research, Croatia.

pain, tolerance, treshold, GWAS

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