engleski

HLA-A, -B, AND -DRB1 alleles and haplotypes and the risk of endemic nephropathy in Croatians.

Aim: Endemic nephropathy (EN) is classified as a tubulointerstitial progressive chronic disease that affects kidneys with a slow clinical course. Disease occurs in rural communities along the river flows of the Danube river basin in Croatia, Bosnia and Herzegovina, Serbia, Bulgaria and Romania. In Croatia, the endemic focal point includes fourteen villages and affects population of about 10 000 people located in the BrodskoPosavska County on the Sava River bank, west of Slavonski Brod. Over the past period, the influence of hereditary and environmental factors on the appearance of EN (heavy metals, microelements, various viruses and bacteria, soil, drinking water, polycyclic hydrocarbons aromatic compounds) were investigated. Recently, next generation sequencing nominated three genes tightly connected to process of angiogenesis as candidate genes for predisposition to Balkan endemic nephropathy, one of them (KCNK5) being located on chromosome 6p21.2, in close proximity to the HLA region. Methods: Prompted by this finding, we investigated HLA-A, -B, and -DRB1 alleles and haplotypes in the population of patients with EN (N=103) and matched healthy controls (N=190). All individuals were tested by PCR-SSO for low resolution typing and PCR-SSP to obtain a high-resolution typing. Results: The results showed higher presence of HLA-DRB1*04:02 allele in EN (P=0.013, OR=3.006, 95% CI=1.28- 7.07), in contrast to the lower frequency of HLA- A*01:01, B*57:01 and B*27:05 alleles (P=0.002, OR=0.373, 95% CI=0.19-0.72 ; P=0.032, OR=0.339, 95% CI=0.13-0.90 and P=0.006, OR=0.098, 95% CI=0.01-0.74, respectively). Moreover, when EN patient’s HLA haplotypes were compared to controls, two haplotypes were present with higher frequency within EN patients group, HLA- A*02:01~B*27:02~DRB1*16:01 and HLA- A*26:01~B*38:01~DRB1*04:02 (P=0.002, OR=0 and P=0.054, OR=4.702, 95% CI=0.90- 24.45, respectively) while HLA-A*02:01~B*57:01~DRB1*16:01 (P=0.031, OR=0) haplotype showed a significantly lower frequency. Two other haplotypes, HLA- A*02:01~B*27:05~DRB1*01:01 and HLAA*01:01~B*57:01~DRB1*07:01, were also less frequent among EN patients, but this difference did not reach statistical significance. Conclusion: The results point toward genetic susceptibility to EN indicating the necessity of further studies.

Endemic nephropathy ; Croatia ; HLA-A, -B, -DRB1

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