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.
Highlights
Introduction e incidence ofEnd-stage renal disease (ESRD) in the world is increasing as well as in Indonesia. e Indonesian Renal Registry showed that ESRD incidence rose from 9649 in 2010 to 30831 in 2017
human leukocyte antigen (HLA) is encoded by the major histocompatibility complex (MHC) located on chromosome 6p21.3. e HLA molecule binds and presents peptide to T lymphocytes in cell-mediated immune response and plays a crucial role in shaping the T-cell repertoire and is associated with allograft rejection [2, 3]. e correlation of HLA polymorphism with ESRD can be caused by HLA association with the aetiology and the progression of kidney
E allele number of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in ESRD patients and donors are summarized in column charts shown in Figure 1. e Hardy–Weinberg Equilibrium (HWE) tests of the HLA-A, -B, -C, -DRB1, -DQB1, and -DRP1 loci showed p > 0.05
Summary
Introduction e incidence ofESRD in the world is increasing as well as in Indonesia. e Indonesian Renal Registry showed that ESRD incidence rose from 9649 in 2010 to 30831 in 2017. End-stage renal disease (ESRD) is suspected to be influenced by genetic and nongenetic factors. Many genetic factors cause ESRD, and human leukocyte antigen (HLA) is an essential factor. E correlation of HLA polymorphism with ESRD can be caused by HLA association with the aetiology and the progression of kidney. In a Mexican population with type 2 diabetes mellitus (T2DM), HLA-DRB1 ∗ 15:02 is associated with diabetic kidney disease. 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. 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
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