Balkan endemic nephropathy (BEN), a progressive chronic tubulointerstitial disease, occurs in the endemic focus of Croatia in a population of about 10,000 inhabitants. One of its most peculiar characteristics is a strong association with upper tract urothelial carcinoma (UTUC). Despite a high number of studies, currently there are insufficient data about the association of BEN and HLA genes. The aim of this study was to investigate the polymorphism of HLA-A, -B, and -DRB1 alleles and haplotypes among BEN patients and to determine whether an association between HLA and BEN exists. In this study, we investigated HLA-A, -B, and -DRB1 alleles and haplotypes in a population of patients with BEN (N = 111) and matched healthy controls (N = 190). All individuals were tested by PCR-SSO and PCR-SSP methods to assess the possible contribution of HLA alleles and haplotypes to the development of/protection from BEN. Our results showed a positive association between the presence of HLA-B*35:02 and DRB1*04:02 alleles and BEN (P = 0.0179 and P = 0.0151, respectively) in contrast to the protective effect of HLA-A*01:01, B*27:05 and B*57:01 alleles (P = 0.0111, P = 0.0330 and P = 0.0318, respectively). Moreover, when BEN patients’ HLA haplotypes were compared to controls, two haplotypes were associated with BEN susceptibility among Croatians (HLA-A*02:01~B*08:01~DRB1*03:01 and HLA-A*02:01~B*27:02~DRB1*16:01, P = 0.0064 and P = 0.0023, respectively), while haplotypes HLA-A*02:01~B*27:05~DRB1*01:01 and HLA-A*02:01~B*38:01~DRB1*13:01 each showed a possible protective effect (P = 0.0495). Our results point toward genetic susceptibility to BEN and observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of this disease.

巴尔干地方性肾病（BEN）是一种进行性慢性肾小管间质疾病，发生在克罗地亚的地方性重点地区，约有10,000名居民。其最独特的特征之一是与上尿路尿路上皮癌（UTUC）的紧密联系。尽管进行了大量研究，但是目前关于BEN和HLA基因的关联的数据不足。这项研究的目的是调查BEN患者中HLA-A，-B和-DRB1等位基因和单倍型的多态性，并确定HLA和BEN之间是否存在关联。在这项研究中，我们调查了BEN（N = 111）和健康对照（N = 190）患者人群中的HLA-A，-B和-DRB1等位基因和单倍型。所有个体均通过PCR-SSO和PCR-SSP方法进行测试，以评估HLA等位基因和单倍型对BEN发生/保护的可能贡献。我们的结果显示，与HLA-A * 01的保护作用相反，HLA-B * 35：02和DRB1 * 04：02等位基因与BEN的存在呈正相关（分别为P = 0.0179和P = 0.0151）： 01，B * 27：05和B * 57：01等位基因（分别为P = 0.0111，P = 0.0330和P = 0.0318）。此外，当BEN患者的HLA单倍型与对照进行比较时，克罗地亚人中有两种单倍型与BEN易感性相关（HLA-A * 02：01〜B * 08：01〜DRB1 * 03：01和HLA-A * 02：01 〜B * 27：02〜DRB1 * 16：01，分别为P = 0.0064和P = 0.0023），而单倍型为HLA-A * 02：01〜B * 27：05〜DRB1 * 01：01和HLA-A * 02：01〜B * 38：01〜DRB1 * 13：01均显示出可能的保护作用（P = 0.0495）。