High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese.
High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese.
复制标题
DOI：
10.1038/srep38189
复制
发表时间：
2016-12-09
影响因子：
4.6
通讯作者：
Noiri E
中科院分区：
文献类型：
--
作者：
Thiri M;Honda K;Kashiwase K;Mabuchi A;Suzuki H;Watanabe K;Nakayama M;Watanabe T;Doi K;Tokunaga K;Noiri E
尽管近年来研究表明抗PLA 2 R抗体在特发性膜性肾病（IMN）中起重要作用，但对IMN中HLA基因的定位及与PLA 2 R1的相互作用尚未见报道。我们对183名IMN患者和811名健康对照者的PLA 2 R1基因和HLA区域进行了基因分型。PLA 2 R1基因周围的5个SNPs与IMN显著相关。除了先前报道的与IMN强相关的两个SNPs，rs3749119和rs35771982，（OR分别为3.02和2.93，P = 3.24E-14和4.64E-14），两个新的内含子SNP（rs 2715928和rs 16844715）也被鉴定为IMN相关SNP（OR分别为2.30和2.51，P = 3.15E-10和5.66E-13）。在HLA基因分析中，DRB 1 *1501和DQB 1 *0602与IMN密切相关（P值分别为1.14 E-11和1.25 E-11）。HLA-DRB 1 *15：01 -HLA-DQB 1 *06：02与内含子SNP rs 2715928之间的相互作用最强（OR = 17.53，P = 4.26E-26）。HLA-DRB 1 *15：01 -HLA-DQB 1 *06：02与IMN的错义SNP rs35771982（OR = 15.91，P = 2.76E-29）和内含子SNP rs 16844715（OR = 15.91，P = 2.30E-26）之间也存在正交互作用。在平均11年的观察期内，HLA-DRB 1 *15：01和HLA-DQB 1 *06：02均与类固醇反应性、总生存率和肾生存率无关，但分析数量有限。
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.
登录
查看更多内容
影响因子：
29.4
作者：
Berntsen, Natalie L.;Klingenberg, Olav;Hov, Johannes Roksund
通讯作者：
Hov, Johannes Roksund
影响因子：
13.6
作者：
Coenen, Marieke J. H.;Hofstra, Julia M.;Ronco, Pierre
通讯作者：
Ronco, Pierre
影响因子：
158.5
作者：
Stanescu, Horia C.;Arcos-Burgos, Mauricio;Kleta, Robert
通讯作者：
Kleta, Robert
影响因子：
4.5
作者：
Fernando MM;Stevens CR;Walsh EC;De Jager PL;Goyette P;Plenge RM;Vyse TJ;Rioux JD
通讯作者：
Rioux JD
影响因子：
3.2
作者：
Tokunaga, K;Ishikawa, Y;Juji, T
通讯作者：
Juji, T