Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease.

IF 7 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Xue Zhang, Yuqing Wang, Huiwen Xue, Yingsuo Zhao, Mingcheng Liu, Hui Wei, Qianwei Liu
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引用次数: 0

Abstract

Background: Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, often remaining asymptomatic until the thyroid is significantly affected. Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to drive many inflammatory diseases and autoimmune diseases. The association between CHIP and AITD is scarcely reported. This study aims to investigate whether CHIP is associated with the risk of AITD.

Methods: We conducted a prospective community-based cohort study at the UK Biobank. CHIP, defined as the exposure, was identified using whole-exome sequencing (WES) data. AITD was sourced from the inpatient hospitalization register, the death register, and the primary healthcare register. Cox regression models were utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between CHIP and AITD. Next, we conducted a subgroup analysis to investigate the role of specific gene mutations (DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2) in the investigated association. Finally, we assessed the association across small CHIP clones (variant allele frequency, VAF: 2-10%) and large CHIP clones (VAF ≥ 10%). All models were adjusted for sex, age, ethnicity, education, Townsend deprivation index, body mass index, smoking status, and drinking status.

Results: A total of 454,618 individuals were included in the final analysis. We identified 14,059 (3.1%) participants with CHIP. Compared with individuals without CHIP, those with CHIP were generally older and more likely to be smokers. Over a median follow-up of 12.7 years (interquartile range, IQR: 11.9-13.5), 21,708 cases with AITD were diagnosed. CHIP was associated with an increased risk of AITD (HR 1.11, 95% CI 1.03-1.19). Specifically, individuals with TET2-mutant CHIP (HR 1.23, 95% CI 1.07-1.41) had an elevated risk of AITD. A large CHIP clone (HR 1.17, 95% CI 1.08-1.27) was associated with an increased risk of AITD. Focusing on large CHIP clone, we also observed an association between TET2-mutant (HR 1.27, 95% CI 1.10-1.47) and ASXL1-mutant (HR 1.33, 95% CI 1.02-1.73) CHIP and risk of AITD.

Conclusions: Individuals with CHIP were associated with a modestly increased risk of AITD, especially TET2-mutant CHIP. Future studies are needed to verify current findings and elaborate potential mechanisms.

自身免疫性甲状腺疾病潜在和风险不确定的克隆造血。
背景:自身免疫性甲状腺疾病(AITD)是最常见的器官特异性自身免疫性疾病,通常在甲状腺受到明显影响之前无症状。不确定电位克隆造血(CHIP)已被报道驱动许多炎症性疾病和自身免疫性疾病。CHIP与AITD之间的关系鲜有报道。本研究旨在探讨CHIP是否与AITD风险相关。方法:我们在英国生物银行进行了一项前瞻性社区队列研究。CHIP,定义为暴露,使用全外显子组测序(WES)数据进行鉴定。AITD来自住院病人登记、死亡登记和初级保健登记。采用Cox回归模型估计CHIP与AITD相关性的风险比(HR)和95%置信区间(CI)。接下来,我们进行了亚组分析,以研究特定基因突变(DNMT3A、TET2、ASXL1、PPM1D、SRSF2和JAK2)在研究关联中的作用。最后,我们评估了小CHIP克隆(变异等位基因频率,VAF: 2-10%)和大CHIP克隆(VAF≥10%)之间的相关性。所有模型都根据性别、年龄、种族、教育程度、汤森剥夺指数、体重指数、吸烟状况和饮酒状况进行了调整。结果:最终分析共纳入454,618人。我们确定了14059名(3.1%)CHIP患者。与没有CHIP的人相比,CHIP患者通常年龄更大,更有可能成为吸烟者。在中位随访12.7年(四分位间距,IQR: 11.9-13.5)期间,诊断出21,708例AITD。CHIP与AITD风险增加相关(HR 1.11, 95% CI 1.03-1.19)。具体来说,tet2突变CHIP的个体(HR 1.23, 95% CI 1.07-1.41)患AITD的风险较高。大CHIP克隆(HR 1.17, 95% CI 1.08-1.27)与AITD风险增加相关。针对大型CHIP克隆,我们还观察到tet2突变体(HR 1.27, 95% CI 1.10-1.47)和asxl1突变体(HR 1.33, 95% CI 1.02-1.73) CHIP与AITD风险之间的关联。结论:CHIP患者与AITD风险适度增加相关,尤其是tet2突变CHIP。未来的研究需要验证目前的发现和阐述潜在的机制。
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
BMC Medicine
BMC Medicine 医学-医学:内科
CiteScore
13.10
自引率
1.10%
发文量
435
审稿时长
4-8 weeks
期刊介绍: BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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