(401) A SNP in COL11A2 associated with thermal hyperalgesia in patients with knee osteoarthritis

Abstract

Hypersensitivity to painful stimuli is a well-recognized phenomenon in patients with knee osteoarthritis(OA). The degree of hypersensitivity is thought to be attributed to individual differences, including the central processing and genetic variability. We hypothesize that there are natural genetic variations within the pain genes affecting the development of such hypersensitivity in patients with knee osteoarthritis. Here we show that the minor allele of rs16868943 in gene COL11A2 is significantly associated with lower arm thermal tolerance in patients with knee OA (P=1.21x10-6, P=0.0053 after Bonferoni correction). This SNP is also nominally associated with other measures of thermal pain hypersensitivity, including lower knee thermal pain tolerance (P=1.14x10-5), lower arm thermal pain threshold (P=0.0039) and lowered knee thermal pain threshold (P=0.003). In this study, a total of 161 knee OA patients were included. After clinical screening, each patient underwent multiple experimental pain modalities, including thermal, punctate and pressure pain applied to the affected knee and the ipsilateral arm. Each patient was genotyped for 4392 SNPs in genes implicated in pain perception, inflammation and mood were included in the analysis. The minor A allele of SNP rs16868943 was found to be significantly associated with lowered arm thermal pain tolerance after correction for age, gender, race and study site. Since minor allele frequency is higher in the African American population (7%) compared to the Caucasian Whites (1.4%), a race-specific analysis was carried out. The same finding remains significant in African Americans, and the trend is similar within Caucasian Whites. To further test whether our finding applies to healthy individuals, an association study was carried out between rs16868943 and arm thermal pain tolerance in 91 healthy individuals. It was found to be non-significant (P=0.12). This finding suggests that the development of thermal hypersensitivity with this SNP is dependent upon the development of knee OA.