タナカ　リョウジロウ   Ryojiro Tanaka   田中　亮二郎    所属   川崎医科大学  医学部 臨床医学　小児科学    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population.
掲載誌名	正式名：Journal of the American Society of Nephrology : JASN 略　 称：J Am Soc Nephrol ISSNコード：15333450/10466673
掲載区分	国外
巻・号・頁	29(8),pp.2189-2199
著者・共著者	Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima,
発行年月	2018/08
概要	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 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10-25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10-9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10-12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10-11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor.Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.
DOI	10.1681/ASN.2017080859
PMID	30012571