Association of HLA‐DR/DQ alleles and haplotypes with nephrotic syndrome

Ramanathan, Aravind Selvin Kumar; Senguttuvan, Prabha; Chinniah, Rathika; Vijayan, Murali; Thirunavukkarasu, Mahesh; Raju, Kamaraj; Dhivakar, Mani; Ravi, Padma Malini; Rajendran, P. Selvi; Krishnan, Jeyaram Illiayaraja; Balakrishnan, K.

doi:10.1111/nep.12669

Cited by 15 publications

(6 citation statements)

References 33 publications

(67 reference statements)

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“…This is consistent with the findings of previous studies, despite some limitations with the ability to do direct comparisons, given that most previous studies of SSNS typed the HLA loci at two-digit resolution. For example, a recent study of children with nephrotic syndrome from South India showed a significant association between SSNS and both DRB1*07 and DQB1*02, as well as with the haplotype DRB1*07-DQB1*02 32 . Interestingly, some of the classic HLA alleles found to be significantly associated with SSNS in the present study have previously been reported to be associated with celiac disease and non-celiac gluten sensitivity 25–29 .…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

Adeyemo

Esezobor

Solarin

et al. 2018

American Journal of Kidney Diseases

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HLA-DQA1 is a risk locus for SSNS, but not SRNS, in African American children, consistent with its role in SSNS risk in children of European, Asian, and African ancestries. There is little evidence of a significant role for the APOL1 high-risk alleles in childhood SSNS in African American children. Refinement of the HLA-DQA1 association identified the critical classic HLA antigen types and amino acids of the HLA-DQ α1 molecule.

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Section: Discussionmentioning

confidence: 99%

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

Adeyemo

Esezobor

Solarin

et al. 2018

American Journal of Kidney Diseases

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“…HLA human leukocyte antigen, SSNSWR steroid-sensitive nephrotic syndrome without recurrence, SDNS steroid-dependent nephrotic syndrome, FRNS frequently relapse nephrotic syndrome. † P < 0.01, ‡ P < 0.001 HLA-BW44, which may affect the efficacy of cyclophosphamide [15,[18][19][20][21][22]30]. Taken together, it suggests an importance of distinguishing race and region in HLA allele research.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a simple comparison of HLA type differences between SSNS patients and healthy controls may exclude the effects of indicators related to disease development and prognosis. Previous studies have highlighted the strong association between HLA and its susceptibility to SSNS [18][19][20][21][22][23]. However, ethnic and regional differences in HLA allele polymorphisms may lead to genetic heterogeneity [24].…”

Section: Introductionmentioning

confidence: 99%

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome

Lü

Wang

et al. 2022

World J Pediatr

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Background Few studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS. Methods A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system. Results Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048–0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified. Conclusions HLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.

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“…Regarding HLA allele frequencies in lieu of steroid res ponsiveness in pediatric NS, the full text was available for two Indian studies 127,128) . One study typed HLA class II alleles at DR and DQ loci and found that the DRβ1*150X DQβ1*060X haplotype was significantly more frequent in SRNS than in SSNS 127) (Table 6).…”

Section: Hla Allele Frequenciesmentioning

confidence: 99%

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

et al. 2021

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Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

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Association of HLA‐DR/DQ alleles and haplotypes with nephrotic syndrome

Cited by 15 publications

References 33 publications

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

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