Genetic susceptibility and validation of angiographic patterns in Takayasu arteritis

IF 6.8 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI:10.1016/j.jaut.2025.103496

Desiré Casares-Marfil , K. Bates Gribbons , Guher Saruhan-Direskeneli , Sema Kaymaz-Tahra , Kaitlin A. Quinn , Fatma Alibaz-Oner , Peter C. Grayson , Haner Direskeneli , Amr H. Sawalha , Peter A. Merkel

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引用次数: 0

Abstract

Background

Prior studies identified subsets of patients with Takayasu arteritis (TAK) based on angiographic patterns of disease in cohorts from India and North America. This study aimed to validate these patterns in a TAK cohort from Turkey and determine the role of genetics in arterial patterns.

Methods

421 Turkish patients with TAK underwent angiography of the aorta and branch vessels, with disease involvement characterized in 13 arterial territories. K-means cluster analysis identified angiographically-based subgroups. 282 patients with TAK from Turkey and 115 European-American patients from North America were genotyped. Approximately 6.5 million SNPs were evaluated in a meta-analysis of both cohorts. Logistic regressions identified genetic associations with angiographic clusters (threshold for association: p-value<1x10⁻⁵). Associated variants were functionally annotated.

Results

Three clusters were identified in Turkish patients, validating the previously-identified cluster pattern. Genome-wide meta-analyses revealed a locus in the solute carrier family gene SLC24A2 in Cluster One as the most significant association (rs2891138, OR = 3.34, p-value = 2.32x10⁻⁷). Several genetic loci were associated with Cluster Two, including in LGALSL (rs883021, OR = 0.43, p-value = 1.00X10⁻⁵), AK4P3 (rs1072778, OR = 0.39, p-value = 4.07X10⁻⁶), and TMEM132B (rs4765045, OR = 3.05, p-value = 6.18X10⁻⁶). The most significant locus associated with Cluster Three was in FRMD6 (rs55692665, OR = 2.79, p-value = 1.11X10⁻⁷). Genetic effects were consistent between the cohorts. Several loci were associated with levels of mRNA expression in arterial tissues. A Cluster Two-associated variant in APBB2 (rs2465578, OR = 0.35, p-value = 6.69x10⁻⁶) showed evidence for chromatin interaction with the NSUN7 promoter and increased aortic NSUN7 expression.

Conclusions

Genetic factors are associated with distinct subsets of TAK defined by angiographic pattern of disease.

查看原文本刊更多论文

高须动脉炎的遗传易感性和血管造影模式的验证。

背景：先前的研究在印度和北美的队列中根据疾病的血管造影模式确定了Takayasu动脉炎（TAK）患者亚群。本研究旨在在土耳其的TAK队列中验证这些模式，并确定遗传学在动脉模式中的作用。方法：421例土耳其TAK患者行主动脉和分支血管造影，疾病累及13个动脉区域。k均值聚类分析确定了基于血管造影的亚组。282例土耳其TAK患者和115例北美欧美患者进行基因分型。在两个队列的荟萃分析中评估了大约650万个snp。Logistic回归确定了与血管造影簇的遗传关联（关联阈值：p值5）。对相关的变体进行了功能注释。结果：在土耳其患者中发现了三个集群，验证了先前确定的集群模式。全基因组荟萃分析显示，集群1中溶质载体家族基因SLC24A2的一个位点是最显著的关联位点（rs2891138, OR = 3.34， p值= 2.32x10-7）。多个遗传位点与聚类2相关，包括LGALSL （rs883021, OR = 0.43， p值= 1.00X10-5）、AK4P3 （rs1072778, OR = 0.39， p值= 4.07X10-6）和TMEM132B （rs4765045, OR = 3.05， p值= 6.18X10-6）。与聚类3相关的最显著位点为FRMD6 （rs55692665, OR = 2.79， p值= 1.11X10-7）。遗传效应在队列之间是一致的。有几个位点与动脉组织中mRNA的表达水平相关。APBB2簇2相关变异（rs2465578, OR = 0.35， p值= 6.69x10-6）显示与NSUN7启动子的染色质相互作用和主动脉NSUN7表达增加。结论：遗传因素与不同的TAK亚群有关，这些亚群由疾病的血管造影模式定义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.