rs1051931 Nonsynonymous Polymorphism of Platelet-Activating Factor Acetylhydrolase Gene PLA2G7 Is Associated with Dysesthesia and Pain Severity After Surgery

Abstract

Platelet-activating factor (PAF) is a potent inflammatory mediator that activates the PAF receptor, which induces additional PAF production. Animal studies have shown that PAF induces inflammatory and neuropathic pain, including dysesthesia, a prodromal symptom of neuropathic pain. However, in humans, the association between PAF and pain remains unknown. Phospholipase A2 Group VII (PLA2G7) hydrolyzes PAF to eliminate PAF activity. The present study investigated the association between the PLA2G7 rs1051931 nonsynonymous polymorphism (T/C, Val379Ala), which decreases the PAF-degrading activity of PLA2G7 in plasma, and postoperative pain-related phenotypes in humans. The study included 303 patients who underwent sagittal split ramus osteotomy at Tokyo Dental College and were assessed for dysesthesia and 332 patients who underwent laparoscopic gynecologic surgery at Juntendo University Hospital and were assessed for postoperative pain using the Numeric Rating Scale (NRS). PLA2G7 rs1051931 was significantly associated with dysesthesia (p = 0.0491) and NRS scores (p = 0.0243). Carriers of the CC genotype of PLA2G7 rs1051931 were more likely to have dysesthesia and higher NRS scores than carriers of the TT + TC genotypes. Carriers of the CC genotype of PLA2G7 rs1051931 reportedly had lower PAF-degrading activity in plasma, thereby increasing the amount of PAF. The increase in PAF possibly leads to dysesthesia and postoperative pain in humans.

Keywords: PAF; PAF-AH; PLA2G7; SNP; dysesthesia; postoperative pain.

Figure 1

Associations between genotypes of PLA2G7 rs1051931 and NRS pain scores in the JUH group. The data are expressed as box and whisker plots. The upper and lower ends of the boxes represent the 75th and 25th percentiles, respectively. Whiskers represent the highest and lowest values. Medians are depicted by solid horizontal lines in the boxes. Mean values are depicted by crosses. Each NRS value is depicted by a red dot. The samples were divided into two groups in the dominant model (TT + TC and CC). TT + TC, n = 64; CC, n = 268; * p < 0.05.