Single nucleotide polymorphism in the COL11A2 gene associated with lowered heat pain sensitivity in knee osteoarthritis

Abstract

Pain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.

Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank

“…It is possible that variants in the COL27A1 gene could eventually affect the quality of the tendons such as strength or flexibility, which might lead to poor tendon function, or their stability of the attachment to the patella, which might also be knee pain related. A recent study has suggested that a collagen gene COL11A2 play a role in pain sensitisation after the development of osteoarthritis 43 . Interestingly, the COL27A1 gene was not mentioned in GWAS on osteoarthritis using the UK Biobank dataset 44 .…”

<p>Downregulation of microRNA-23b-3p alleviates IL-1β-induced injury in chondrogenic CHON-001 cells</p>

“…COL11A2 is a member of the fibrillar collagen subgroup, which encodes α chains of type XI collagen 11. It has been reported that COL11A2 may associate with pain sensitivity in OA 12…”

T118M Variant of PMP22 Gene Presents with Painful Peripheral Neuropathy and Varying Charcot-Marie-Tooth Features: A Case Series and Review of the Literature

“…Genetic factors are known to impact pain perception and formation. Common genetic polymorphisms have been shown to affect the development and perception of pain [20, 21]. Rare, single-gene variants causing painful phenotype are less common [22–24].…”