engleski

Association of HLA-A, -B and-DRB1 genes with endemic nephropathy and urothelial carcinoma of upper urinary tract in Croatia.

Introduction & Objectives: Endemic nephropathy (EN) is a chronic tubule interstitial renal disease. Studies made over the years have shown that EN is associated with the development of cancer of the upper urinary tract (UUC). The aim of the study was to investigate the differences in HLA-A, -B, and -DRB1 genes between EN patients both with and without the UUC and the controls and to answer the question whether the HLA genes play susceptible or protective role for the development of EN. Materials & Methods: The study included 89 patients aged 58-88 years divided into 2 subgroups (39 with UUC and 50 patients without UUC) and 150 healthy unrelated individuals from the same region as controls. All subjects were tested for HLA genes by Polymerase Chain Reaction - Sequence Specific Oligos (PCR-SSO) method. HLA frequencies were determined by direct counting. Statistical significance of difference in gene frequencies was calculated using Fisher’s exact test with P value of 0.05 being considered significant. Results: The frequency of HLA genes at tested loci in the present study was similar to that observed for the control group. On the HLA-A locus, only HLA-A*26 specificity was significantly increased among the whole group of patients with EN when compared with controls (P=0.0407), but significance was lost when compared with two subgroups. For the HLA-B locus, there was a decrease in frequency of HLA- B*51 in the EN group (P=0.0399). HLA-B*27 was the only specificity that differed significantly between the patients without UCC and the controls (P=0.0094) and also between the two subgroups with and without UCC (P=0.0027). On the HLA-DRB1 locus, the difference was seen for the HLA-DRB1*16 gene which was significantly increased in the entire EN group when compared with controls (P=0.0230) and also in the subgroup without UUC when compared with controls (P=0.0360). Conclusions: The study of genetic aetiology of endemic nephropathy and urothelial cancer of the upper urinary tract will contribute to better understanding of the mechanisms of these diseases. In the future this should enhance a new way of prevention and therapy. The presence of susceptible HLA genes like HLA-A*26 and -DRB1*16 among family members will point out the healthy subjects with increased risk to developed disease and to include them in the program of preventive examinations while HLA- B*51 may serve as a marker with a protective role.

endemic nephropathy ; urothelial carcinoma ; HLA-DRB1 genes ; Croatia

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