Evaluation of two functional CD24 polymorphisms in primary sclerosing cholangitis

Question:

Primary sclerosing cholangitis (PSC) is a progressive liver disease and characterized by a chronic inflammation, consecutive sclerosis and strictures of the bile ducts. Several genetic risk factors have been described, that might in part contribute to pathogenesis. Functional single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of several autoimmune and autoinflammatory diseases and might contribute to the susceptibility for inflammatory bowel disease (IBD). We aimed to assess the impact of two common CD24 gene polymorphisms on clinical features and disease progression in patients with PSC.

Methods:

PSC patients that were treated at our tertiary center between 1987 – 2016 were included into the study. The final study cohort comprises of 359 PSC patients. Two functional CD24 polymorphisms, a C to T coding polymorphism (rs8734) and a TG deletion in the 3'- untranslated region (rs3838646), were genotyped by restriction fragment length polymorphism (RFLP) and melting curve analysis (MCA). Clinical and laboratory parameters were collected by chart review.

Results:

For the rs8734 genotype, 175 patients (52.2%) were found to be wildtype ("Ala/Ala"), 127 (37.9%) patients were heterozygous ("Ala/Val") and 33 patients (9.9%) were homozygous-mutated ("Val/Val"). Patients carrying homozygous-mutated allels of the rs8734 genotype had less frequent dominant strictures at diagnosis of PSC (p= 0.04). For the rs3838646 genotype, 322 patients (89.7%) were found to be wildtype ("TG/TG") and 37 showed the "TG/del" genotype (10.3%). The "TG/del" genotype was associated with a lower risk of inflammatory bowel disease (p= 0.01). We found no association of any genotype with the development of a cholangiocarcinoma, gall bladder carcinoma (GBC) or colorectal cancer (CRC). There was no significant difference regarding the combined clinical end point death and liver transplantation or overall survival for both genotypes (rs3838646: p= 0.8; rs8734: p= 0.4).

Conclusion:

We found a mild association of the rs8734 CD24 genotype with dominant strictures at first diagnosis of PSC. The rs3838646 CD24 genotype is associated with a lower rate of inflammatory bowel disease in PSC patients. Both SNPs seem to modulate the clinical phenotype without major pathogenetic importance for disease progression in PSC.