Dataset Information

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

ABSTRACT:

Background

The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS.

Methods

In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population.

Results

Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene.

Conclusions

This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

SUBMITTER: Zhu B

PROVIDER: S-EPMC6430441 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

Zhu Bingbing B Zhang Ruifeng R Yang Huandan H Yuan Tingting T Lv Juan J Peng Qianqian Q Tian Lijun L

Journal of clinical laboratory analysis 20180713 1

<h4>Background</h4>The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS.<h4>Methods</h4>In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clin ...[more]

PMID: 30006974

Similar Datasets

Project description:BackgroundFew data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.Study designCase-control study.Setting & participantsAfrican American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium.FactorGenetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles.OutcomesSSNS and SRNS.MeasurementsDirect sequencing for the HLA-DQA1 and APOL1 variants in 115 African American children (65 with SSNS and 50 with SRNS). Imputation of classic HLA alleles and amino acids was done in 363 South Asian children.ResultsThe 2 HLA-DQA1 variants were significantly associated with SSNS in African American children (C34Y: P=5.7 × 10-11; OR, 3.53; 95% CI, 2.33-5.42; F41S: P=1.2 × 10-13; OR, 4.08; 95% CI, 2.70-6.28), but not with SRNS (C34Y: P=0.6; F41S: P=0.2). APOL1 high-risk variants were not associated with SSNS (P=0.5) but showed significant associations with SRNS (P=1.04 × 10-7; OR, 4.17; 95% CI, 2.23-7.64). HLA-DQA1*0201, HLA-DQB1*0201, and HLA-DRB1*0701 were the classic HLA alleles with the most significant associations with SSNS risk. The most significantly associated amino acid positions were HLA-DQα1 56 and 76 (both P=2.8 × 10-7). Conditional analysis revealed that these variants most likely account for the observed association.LimitationsModest sample size and limited statistical power to detect small to moderate effect sizes. Children studied may not be representative of all African American children in the United States.ConclusionsHLA-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.

Project description:BackgroundManagement of patients with steroid-sensitive nephrotic syndrome (SSNS) is challenging because of frequent relapses. Causal variants in the human leukocyte antigen (HLA) class II region that are associated with relapse remain undetermined.MethodsWe collected a cohort of East Asian individuals comprising 206 pediatric patients with SSNS and 435 healthy controls from Southwest China. Ninety children with steroid-sensitive nephrotic syndrome without relapse (SSNSWR) and 116 children with steroid-dependent and/or frequent relapse nephrotic syndrome (SDNS/FRNS) were genotyped using Sanger sequencing. We then measured the transcriptional level, allele expression imbalance (AEI) and functional proteins of HLA-DQA1 and HLA-DQB1 in different stages of SDNS/FRNS.Resultsrs1464545187 in ANKRD36 was associated with an approximately 1.69-fold greater risk for SSNSWR (P = 0.04; 95% confidence interval [CI], 1.05-2.72). Clustered risk variants in HLA-DQA1 and HLA-DQB1 were significantly associated with SDNS/FRNS (rs1047989: P = 2.26E-07, odds ratio [OR] = 2.25, 1.65-3.05; rs9273471: P = 5.45E-05, OR = 1.84, 1.37-2.46; HLA-DQB1*06:02: P = 0.017, OR = 0.19, 0.04-0.77). The genotype distributions of rs1047989, 2:171713702, rs1049123, rs9273471, and HLA-DQB1*06:02 in patients with SSNS were significantly different from those in healthy controls. rs1047989 (HLA-DQA1) was significantly associated with a greater number of infections at relapse in SDNS/FRNS patients (P = 0.045, OR = 6.79, 95% CI: 1.29-168.52). Flow cytometry showed that the proportion of cells expressing HLA-DQA1+/DQB1+ (HLA-DQA1+, P = 0.0046; HLA-DQB1+, P = 0.0045) was lowest in the relapse stage. In addition, the mRNA levels of HLA-DQA1 and HLA-DQB1 were significantly greater in the relapse group than in the remission group (HLA-DQA1, P = 0.03; HLA-DQB1, P = 0.002). No significant AEIs were detected in the different stages of SDNS/FRNS. The rs1047989 variant is likely to affect the structure and stability of HLA-DQA1.Conclusionrs1464545187 is a risk locus for SSNSWR but not SDNS/FRNS in Chinese children. Functional variations in HLA-DQA1 and HLA-DQB1 are implicated in regulating the immune response of SSNS patients, which may explain the typical triggering of SDNS/FRNS onset by infections.

Project description:BACKGROUND AND OBJECTIVES: Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ ?-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed. RESULTS: This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. CONCLUSION: This study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.

Dataset Information

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

Background

Methods

Results

Conclusions

Publications

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets