engleski

Association of HLA alleles and haplotypes with endemic nephropathy in Croatia.

Endemic nephropathy (EN) is a chronic kidney disease affecting populations in several countries, with an endemic focus in eastern Croatia with a population of about 10, 000 people. EN is a multifactorial disease with polygenic predis position to environmental risk agents. Recently, next generation sequencing nominated three genes tightly connected to process of angiogenesis as candidate genes for predispos tion to Balkan endemic nephropathy, one of them (KCNK5) being located on chromosome 6p21.2, in close proximity to the HLA region. Prompted by this finding, we investigated HLA-A, - B, and -DRB1 alleles and haplotypes in the popu lation 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. 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 patient 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) haplo- type showed a significantly lower frequency. HLA- A*02:01~B*27:05~DRB1*01:01 and HLA-A*01:01~B* 57:01~DRB1*07:01 haplotypes were also less frequent among EN patients but this difference did not reach statistical significance. In conclusion, our results point toward genetic susceptibility of EN and observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies.

HLA ; endemic nephropathy ; Croatia

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