Polymorphism of HLA-DRB1 genes among patients with endemic nephropathy and urothelial carcinoma of upper urinary tract in the Croatian population

Damir Dittrich¹, Marija Maskalan², Renata Žunec², Željko Kaštelan³, Zorana Grubić²
¹ General Hospital “Dr. Josip Benčević”, Department of Urology
² Tissue Typing Center, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb
³ University Hospital Centre Zagreb, Department of Urology

Endemic nephropathy (EN) is a chronic tubulointerstitial renal disease associated with the development of cancer of the upper urinary tract (UUC). The Human Leukocyte Antigen (HLA) plays role in immune response and its genes are involved in aetiology of autoimmune diseases as well as in carcinomas.
The aim of this study was to investigate the differences between EN patients with and without UUC and HLA-DRB1 genes.

Materials and methods:
The study included 85 patients aged 58-88 years, with EN, treated at the Urology Department and Dialysis Department, General Hospital “Dr.Josip Benčević” Slavonski Brod, in the period from 2005 to 2018, and 150 healthy matched controls.
Peripheral blood of all patients and controls was collected for HLA typing. All individuals were tested for HLA-DRB1 genes using Polymerase Chain Reaction – Sequence Specific Oligos (Luminex technology).

Thirteen different HLA-DRB1 genes were observed among EN patients as well as among controls. The most frequent HLA-DRB1 gene in patient’s group was HLA-DRB1*11 (20.7%), while among controls two HLA-DRB1* genes (DRB1*11 and DRB1*16 were observed with the same frequency (15.9%, each).
Comparison between tested groups revealed significant P value for DRB1*16 which was significantly more present among patients in comparison to controls (15.9% vs. 8.3%; P=0.0144).

Our preliminary data demonstrated existence of positive association between DRB1*16 gene and EN in our population. The obtained data needs to be confirmed in future studies which should also investigate the distribution of HLA-DRB1 genes among patients with and without UUC, and include other HLA genes.