Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population

Journal of the American Society of Nephrology : JASN
Xiaoyuan JiaResearch Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in Japan

Abstract

Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown.Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay.Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10-23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to ...Continue Reading

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Nov 18, 2018·Clinical Journal of the American Society of Nephrology : CJASN·Howard Trachtman
Jul 3, 2019·Journal of the American Society of Nephrology : JASN·Stephanie DufekDetlef Bockenhauer
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Jan 11, 2022·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Tomoko HorinouchiKazumoto Iijima

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