Genome-wide association analysis reveals the associations of NPHP4, TYW1-AUTS2 and SEMA6D for Behcet's disease and HLA-B*46:01 for its intestinal involvement

被引：3

作者：

Jung, Eun Suk ^{[1
,2
,3
,4
]}

Ellinghaus, David ^{[3
,4
,10
]}

Degenhardt, Frauke ^{[3
,4
]}

Meguro, Akira ^{[5
]}

Khor, Seik-Soon ^{[6
]}

Mucha, Soeren ^{[3
,4
]}

Wendorff, Mareike ^{[3
,4
]}

Juzenas, Simonas ^{[3
,4
,7
]}

Mizuki, Nobuhisa ^{[5
]}

Tokunaga, Katsushi ^{[6
]}

Kim, Seung Won ^{[1
,2
]}

Lee, Min Goo ^{[8
]}

Schreiber, Stefan ^{[3
,4
]}

Kim, Won Ho ^{[1
,2
]}

Franke, Andre ^{[3
,4
]}

Cheon, Jae Hee ^{[1
,2
,9
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Internal Med, 50-1 Yonsei Ro, Seoul 03722, South Korea

[2] Yonsei Univ, Inst Gastroenterol, Coll Med, Seoul, South Korea

[3] Univ Kiel, Inst Clin Mol Biol, Rosalind Franklin Str 12, D-24105 Kiel, Germany

[4] Univ Med Ctr Schleswig Holstein, Rosalind Franklin Str 12, D-24105 Kiel, Germany

[5] Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Yokohama, Japan

[6] Natl Ctr Global Hlth & Med, Genome Med Sci Project, Tokyo, Japan

[7] Vilnius Univ, Inst Biotechnol, Life Sci Ctr, Vilnius, Lithuania

[8] Yonsei Univ, Severance Biomed Sci Inst, Dept Pharmacol, Brain Korea PLUS Project Med Sci 21,Coll Med, Seoul, South Korea

[9] Yonsei Univ, Coll Med, Dept Internal Med, 50-1 Yonseiro,Seodaemungu, Seoul 03722, South Korea

[10] Univ Kiel, Univ Med Ctr Schleswig Holstein, Inst Clin Mol Biol, Campus Kiel,Rosalind Franklin Str 12, D-24105 Kiel, Germany

来源：

DIGESTIVE AND LIVER DISEASE | 2024年 / 56卷 / 06期

关键词：

Behcet's disease; Genome-wide association study; HLA-B*46:01; Intestinal Behcet's disease; MYCOBACTERIUM-AVIUM; CLASS-I; GENE; COMPLEX; NEPHRONOPHTHISIS; IL23R-IL12RB2; DIAGNOSIS; RESPONSES; ENCODES; CHINESE;

D O I：

10.1016/j.dld.2023.10.021

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Intestinal involvement in Behcet's disease (BD) is associated with poor prognosis and is more prevalent in East Asian than in Mediterranean populations. Identifying the genetic causes of intestinal BD is important for understanding the pathogenesis and for appropriate treatment of BD patients. Methods: We performed genome-wide association studies (GWAS) and imputation/replication genotyping of human leukocyte antigen (HLA) alleles for 1,689 Korean and Turkish patients with BD (including 379 patients with intestinal BD) and 2,327 healthy controls, followed by replication using 593 Japanese patients with BD (101 patients with intestinal BD) and 737 healthy controls. Stratified cross-phenotype analyses were performed for 1) overall BD, 2) intestinal BD, and 3) intestinal BD without association of overall BD. Results: We identified three novel genome-wide significant susceptibility loci including NPHP4 (rs74566205; P=1.36 x10(-8)), TYW1-AUTS2 (rs60021986; P=1.14 x10(-9)), and SEMA6D (rs4143322; P= 5.54 x10(-9)) for overall BD, and a new association with HLA-B* 46:01 for intestinal BD (P= 1.67 x10(-8)) but not for BD without intestinal involvement. HLA peptide binding analysis revealed that Mycobacterial peptides, have a stronger binding affinity to HLA-B* 46:01 compared to the known risk allele HLA-B* 51:01. Conclusions: HLA-B* 46:01 is associated with the development of intestinal BD; NPHP4, TYW1-AUTS2, and SEMA6D are susceptibility loci for overall BD. (c) 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

引用

页码：994 / 1001

页数：8

共 61 条

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