Osteoporosis / Osteopoenia in Crohn's disease patients expressing the ATG16L1 gene variants

Abstract

Introduction: Recent studies have established a link between osteoporosis and the autophagy pathway. This pathway is also in part responsible for the mucosal inflammation seen in Crohn's disease. The autophagy ATG16L1 rs2241880 polymorphism is a susceptibility gene for Crohn's disease whose role in bone metabolism has not been studied so far. Aim & Method: To evaluate whether Crohn's disease patients with the ATG16L1 rs2241880 polymorphism have lower bone mineral densities (BMD) than Crohn's patients not exhibiting this polymorphism. Secondary aims include to establish whether there are significant differences in the rs2241880 polymorphism between Maltese Crohn's and control populations and to investigate the risk factors which are associated with lower bone mineral densities in Maltese Crohn's disease patients. Whole blood from 101 Crohn's disease patients and 95 random controls was collected. DNA was extracted from blood and the common coding variant rs2241880 (Thr300Ala) of the ATG16L1 gene was assessed through quantitative polymerase chain reaction, high resolution melt and restriction fragment length polymorphism using the SfaNI/LweI enzyme. All Crohn's disease patients underwent a bone density scan. Results: There was no statistically significant difference in T scores at the hip (p: 0.092), T score at the spine (p: 0.483), Z score at the hip (p: 0.225) and Z score at the spine (p: 0.727) between patients with wild type and mutant A TG 16L1 rs2241880 variants, though patients with the wild type variant had higher T scores than patients with the heterozygous and homozygous rs2241880 polymorphism. There was no statistically significant difference in the prevalence of the rs2241880 polymorphism between Maltese Crohn's disease and control populations (x2 p: 0.093). Low body mass index, the need for surgical intervention and treatment with the biological agent infliximab were shown to be significantly associated with lower BMD scores in Crohn's disease. Conclusion: The rs2241880 polymorphism of the autophagy gene ATG16L1 is not significantly associated with lower BMD scores in Crohn's disease, though patients with the polymorphism had lower DEXA T scores at the hip and spine than those who did not carry the polymorphism. Further studies on the role of autophagy in bone metabolism may suggest new therapeutic mechanisms in bone diseases.