The Link Between Low Back Pain And Diabetes: Gene-Based Association Study In People With Comorbid Diabetes Mellitus And Low Back Pain

Purpose Diabetes mellitus type 2 is a disease associated with chronic pain. Mechanisms of this association are not fully understood. Few studies have explored the genetics of this association, and an independent genetic link between diabetes and low back pain (LBP) has not been completely investigated. We hypothesize that variants in candidate genes are associated with comorbid diabetes and LBP phenotypes. Methods This cross-sectional study is a part of a larger study of subacute and chronic LBP within the PRECISION Pain Research Registry. Subjects were recruited from the Dallas–Fort Worth Metroplex and reported LBP for at least 2 months (subacute) or 6 months (chronic) for half or more of the days with the relevant time period. Primary outcomes were assessed using a Numerical Rating Scale (NRS) for pain intensity, the Roland-Morris Disability Questionnaire for back-specific functioning, and the Patient-Reported Outcomes Measurement Information System (PROMIS) for quality of life measures. Study participants self-reported diabetes. Biological samples were collected to determine participants’ genotypes using the Infinium Global Screening Array. Analyses were conducted using SPSS among 488 study participants, 109 of whom reported diabetes. Twenty-seven candidate genes concurrently implicated in both pain phenotypes and diabetic phenotypes were identified from the literature. These candidate genes were used to perform a gene-based association study (GBAS) to identify their potential association with diabetes and LBP. Genetic variants were mapped to candidate genes for association with each of the pain phenotypes after adjusting for age, sex, diabetes status, and ancestry components 1-10 using MAGMA. Results GBAS results point to variants in the PRKCA gene as being associated with both NRS of LBP intensity and diabetes. PRKCA is a family of protein kinases implicated in neuropathic pain and formation of advanced glycation end products. Conclusions Of the 27 genes tested, only variants in PRKCA are significantly associated with LBP and diabetes in the PRECISION cohort. These findings build on a framework which suggests that genetic predisposition in PRKCA may underlie diabetes and LBP.