Pain perception genes, asthma, and oral health: A reverse genetics study

Abstract

Pain is an experience of a subjective nature, interpreted in a personal way and according to an extensive palette of factors unique to each individual. Orofacial pain can be acute or chronic and it is usually the main reason for the patient to seek dental care. Pain perception varies widely among individuals. This variability is considered a mosaic of factors, which include biopsychosocial factors and genetic factors. Understanding these differences can be extremely beneficial for pain management in a personalized and more efficient way. We performed association studies to investigate phenotypes associated with genetic markers in pain-related genes in two groups of patients who received more or less anesthesia during dental treatment. The study group was comprised of 1289 individuals participating in the Dental Registry and DNA Repository Project (DRDR) of the University of Pittsburgh, with 900 participants in the group that received the most anesthesia and 389 constituting the comparison group that received less anesthesia. We tested 58 phenotypes and genotypic data of seven SNPs in genes that are associated with pain perception, pain modulation and response to drugs used in pain treatment: COMT (rs4818 and rs6269), GCH1 (rs3783641), DRD2 (rs6276), OPRM1 (rs1799971), SCN9A (rs6746030) and SCN10A (rs6795970). The analysis revealed a protective effect of rs1799971 on asthma in the total sample. rs3783641 was associated with salivary secretion disorders in females who received more anesthesia. rs1799971 was also associated with periodontitis in Whites who received less anesthesia. rs4818 was associated with disease and other tongue conditions in the group composed of Blacks who received less anesthesia. In conclusion, our study implicated variants in pain-related genes in asthma and oral phenotypes.

Fig 1. Overall study design flowchart.

The stages of the study are presented from the selection of groups from the Dental Registry and DNA Repository (DRDR) to the PheWAS analysis.

Fig 2. PheWAS results stratified across different groups.

The color red represents a group of individuals that received more anesthesia. Blue represents a group that received less anesthesia, and green represents the total sample. The tip direction of the triangles represents the direction of the odds ratio of each association, the upward triangles indicate OR ≥ 1; downward triangles indicate a protective effect (OR < 1.0). Nominal associations are showed under the horizontal red line that indicates threshold of p < 0.002.

Fig 3. PheWAS result for SNP rs1799971 performed with the total sample.

The blue line indicates p-value <0.05. The horizontal red line indicates the threshold of p < 0.002. The tip direction of the triangles represents the direction of the odds ratio of each association, the upward triangles indicate odds ratio≥1; downward triangles indicate a protective effect (odds ratio<1.0). The different colors of the triangles indicate different disease groups.