Evaluation of Human Leukocyte Antigen Class I and Class II in End-Stage Renal Disease Occurrence in Indonesian Transplantation Patients

Abstract

Background. Genetic studies of end-stage renal disease (ESRD), including those of human leukocyte antigen (HLA) genes, have been reported in several populations but have not yet been evaluated in Indonesia. Some studies have reported that these genes had a substantial role in ESRD. This study aims to analyze the association between HLA genes and ESRD within the Indonesian community. Method. A retrospective study to investigate HLA class I and II alleles to find out the distribution of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 in renal transplant recipients and to ascertain their role in susceptibility to ESRD was performed on totally 149 subjects, consisting of 69 ESRD patients and 80 healthy controls. HLA typing was determined using Luminex techniques. The allele and haplotype frequencies were compared between ESRD patients and controls. Result. High-frequency alleles were HLA-A ∗ 24 (43.6%), B ∗ 15 (38.2%), C ∗ 08 (30.8%), DRB1 ∗ 12 (47.3%), DQB1 ∗ 03 (50.6%), and DPB1 ∗ 13 (22.5%). HLA-A ∗ 24 p = 0.01 and HLA-B ∗ 35 p = 0.02 were associated with a protective effect, with OR 0.537 (95%CI 0.34–0.86) and 0.316 (95%CI 0.11–0.88), respectively. There were some two-locus haplotypes associated with susceptibility to ESRD, such as B ∗ 15-DRB1 ∗ 12, B ∗ 13-DRB1 ∗ 15, A ∗ 02-B ∗ 15, A ∗ 02-C ∗ 08, and B ∗ 13-DQB1 ∗ 05. HLA-A ∗ 02-B ∗ 15-DRB1 ∗ 12 and A ∗ 24-B ∗ 13-DRB1 ∗ 15 appear to be associated with susceptibility to ESRD. Conclusion. The allele groups of HLA-A ∗ 24 and HLA-B ∗ 35 are associated with protection from ESRD. Meanwhile, HLA-B ∗ 13-DRB1 ∗ 15 and A ∗ 24-B ∗ 13-DRB1 ∗ 15 are the most frequent HLAs associated with ESRD in two-locus and three-locus haplotype, respectively.

Association between End-stage renal disease and the polymorphism of HLA in Guangxi Zhuang population

“…We [10]. Based on the HLA and ESRD data presented above, the results were contradictory and inconsistent, which may be related to the polymorphism of HLA across regions and races or require more research [21].…”

“…Our investigation was conducted without consideration for primary renal disease resulting in ESRD, as in some described studies [21][22][23][24][25]27], which is our study's one limitation. The other main limitations of this study were the small number of HLA loci and the patient sample size, which called for further research with larger patient samples, more HLA loci, and every condition that could cause ESRD.…”

“…However, susceptible alleles should receive more attention because they are signi cantly more common in ESRD patients than controls, making it more di cult to match patients with kidney transplants.In some studies, HLA alleles and ESRD are signi cantly correlated, but most research uses low-resolution HLA typing. HLA-A*24 and HLA-B*35 may be protective alleles for patients with ESRD in Indonesia[21]; HLA-B*50 may be susceptible to ESRD in Pakistan, whereas HLA-B*40, DRB1*13, and DRB1*12 may be protective alleles for patients with ESRD[22] ; HLA-DRB1*4 and DRB1*11 may be susceptible alleles for patients with ESRD in the Henan Han population of China, whereas HLA-B*62 and DRB1*15 may be protective alleles for patients with ESRD[23]; HLA-B8 may be a susceptible allele to ESRD in Kuwaiti patients, and HLA-A28 and HLA-DR11 may be protective alleles for patients with ESRD[24]; HLA-A2, -B48, -B52, and -B55 were positively associated with ESRD in the Hunan Han population of China, whereas HLA-B60 was negatively associated with ESRD[25];HLA-A*24, B*54, B*55, B*60, and DRB1*04 may be susceptible alleles to ESRD in Chinese Cantonese patients with ESRD[26]; HLA-B*15 and B*18 may be susceptible alleles to ESRD in Saudi Arabian patients, whereas HLA-A*26, B*39, and B*50 may be protective alleles for patients with ESRD[27]; DRB1*03 and DRB1*11 in Taiwanese were markers for ESRD development…”

Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania

“…In recent years, the association between HLA alleles and ESRD has been suggested, as several HLA class I and class II alleles were found to either be protective or risk factors for ESRD in various studies worldwide. Therefore, genetic association studies conducted in different populations are essential for providing more evidence on globally susceptible HLA alleles and for identifying new alleles associated with particular ESRD patients in a country or area [16]. Although many ESRD-associated HLA alleles have been reported, the results of various studies are inconsistent [17].…”