title: High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese.
abstract: Although recent studies showed anti-PLA2R antibody plays a crucial role in idiopathic membranous nephropathy (IMN), detailed HLA mapping and interaction between the HLA genes and PLA2R1 have not been investigated in IMN. We genotyped across the PLA2R1 gene and the HLA region, using 183 IMN patients and 811 healthy controls. Five SNPs around the PLA2R1 gene were significantly associated with IMN. In addition to the two SNPs previously reported to be strongly associated with IMN, rs3749119 and rs35771982 (OR 3.02 and 2.93, P = 3.24E-14 and 4.64E-14, respectively), two novel intronic SNPs (rs2715928 and rs16844715) were also identified as IMN-associated SNPs (OR = 2.30 and 2.51, P = 3.15E-10 and 5.66E-13, respectively). In the HLA gene analysis, DRB1*1501 and DQB1*0602 were strongly associated with IMN (P = 1.14E-11 and 1.25E-11, respectively). The interaction was strongest between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the intronic SNP rs2715928 (OR = 17.53, P = 4.26E-26). Furthermore, positive interaction was also observed between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the missense SNP rs35771982 (OR = 15.91, P = 2.76E-29), which is in strong linkage disequilibrium with 5'UTR SNP rs3749119, and intronic SNP rs16844715 (OR = 15.91, P = 2.30E-26) for IMN. Neither HLA-DRB1*15:01 nor HLA-DQB1*06:02 was associated with steroid responsiveness, overall survival and renal survival during the observation period of mean 11 years though limited number of analysis.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Myo
authors.initials: M
authors.lastname: Thiri
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Honda
authors.affiliation: Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Mabuchi
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hodaka
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.|Department of Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
mesh_terms: D000368:Aged; D044466:Asian People; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054507:Receptors, Phospholipase A2 / Q000235:genetics*; D015996:Survival Rate
chemical_list: D006680:HLA Antigens; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2