LAUSR

BACKGROUND The prevalence of inflammatory bowel diseases is uprising in countries like Iran. Genetic predisposing elements play prominent role in the pathogenesis of Crohn's disease. In this study we studied the role of autophagy genes like IRGM (Immunity related GTPase M) and ATG16L1 (Autophagy related 16 like 1) in the pathogenesis of Crohn's Disease in Iranian patients. METHODS One hundred thirty-eight patients and 99 normal controls were recruited in this study. Polymorphisms in -1644 and -308 upstream of IRGM gene were studied by PCR-sequencing and 20 kb CNVdel/insertion was studied by specific PCR. Rs10065171, rs4958847 in IRGM gene and rs2241880 in ATG16L1 were studied by Taqman genotyping assays. RESULTS None of the so-called predisposing alleles of IRGM gene predispose Iranians to Crohn's disease while the prevalence of some of them like CNV deletion was higher in normal controls. Surprisingly all the so-called predisposing alleles in IRGM were linked to each other (especially rs4958847 with rs10065172 and polymorphisms in -308 region with rs4958847). Patients harboring A allele in rs4958847 site showed higher ratio of fibrostenotic type of disease while in patients with C/T genotype in rs4958847, colonic involvement was seen more frequently. G allele in ATG16L1 was associated with Crohn's disease though it was not associated with any phenotypic manifestation. CONCLUSION In our study the association of ATG16L1 to Crohn's disease in Iranian patients was confirmed while it was shown that the studied polymorphisms in IRGM was not associated with Crohn's disease. Therefore in order to have a better picture about the genetics of Crohn's disease in Iranian patients, it is recommended to study other clinically effective polymorphisms in IRGM and ATG16L1 in addition to other genes which are responsible for the process of autophagy.