Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Abstract

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = -0.134; p = 0.0490), COX1.3 (R = -0.1429; p = 0.0400) and COX1.5 (Rs = -0.1499; p = 0.032). The expression of COX1.1 (Rs = -0.098; p = 0.049) and COX1.5 (Rs = -0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = -0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

Keywords: CRSwNP; NSAIDs; PTGS1 gene; PTGS2 gene; chronic rhinosinusitis with nasal polyps; cyclooxygenase-1; cyclooxygenase-2; non-steroidal anti-inflammatory drugs; prostaglandin-endoperoxide synthase 1 gene; prostaglandin-endoperoxide synthase 2 gene; transcript variant.

Figure 1

Comparison of PTGS1 (a) and PTGS2 (b) genes transcript variants expression in the study (N = 206) and control (N = 203) groups of patients. The graphs reveal the most common expression profile of transcript variant (the more outside the graph, the more often the specific variant in a given group was observed). COX1.1-COX1.5 and COX2.1-COX2.3 refers to transcript variants of PTGS1 and PTGS2 genes.

Figure 2

Correlations between expression of COX1.1 transcript variant and disease severity. Higher dCt values represent lower expression, hence a negative correlation with dCt represents a positive association between expression of a given variant and disease severity.