家族性和散发性特发性肺纤维化的MMP19变异。

IF 4.6 2区 医学 Q1 RESPIRATORY SYSTEM
Lung Pub Date : 2023-12-01 Epub Date: 2023-11-16 DOI:10.1007/s00408-023-00652-4
Yali Fan, Chunming Zheng, Ruimin Ma, Jingwei Wang, Shuqiao Yang, Qiao Ye
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引用次数: 0

摘要

背景:基因变异已在家族性或散发性特发性肺纤维化(IPF)患者中被发现。这些变异可能部分解释了IPF的遗传风险。本研究的目的是确定家族性和散发性IPF的潜在基因。方法:在这项观察性研究中,对中国北方一个四人诊断为IPF的汉族家庭进行了调查。全外显子组测序(WES)用于鉴定该家族5个成员的潜在疾病表型的种系变异。候选罕见变异通过Sanger测序在来自16名家庭成员和119名散发性IPF患者的样本中进行验证。在16名家族成员、119名其他散发性IPF患者和120名年龄和性别匹配的健康对照中,也检测了上述候选基因编码的血浆蛋白水平。结果:在一个汉族家庭中,MMP19 c.1222在所有家族性IPF患者和来自第三代和第四代的6个后代中发现了C >t。该变异引入了一个过早停止密码子,可能会损害蛋白质功能。Sanger测序显示,7.6%(9/119)的散发性IPF患者携带三种MMP19变体。肺纤维化遗传风险分析显示MMP19 c.1499C > T和C 1316g > A与IPF发病风险增加显著相关(OR为3.66,p = 0.028, OR为8.64,p)结论:家族性或散发性IPF中存在MMP19变异,可能为IPF发病提供新的线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

MMP19 Variants in Familial and Sporadic Idiopathic Pulmonary Fibrosis.

MMP19 Variants in Familial and Sporadic Idiopathic Pulmonary Fibrosis.

Background: Gene variants have been identified in patients with familial or sporadic idiopathic pulmonary fibrosis (IPF). These variants may partially account for the genetic risk of IPF. The aim of this study was to identify potential genes involved in both familial and sporadic IPF.

Methods: A Han family in northern China with four members diagnosed with IPF was investigated in this observational study. Whole-exome sequencing (WES) was used to identify germline variants underlying disease phenotypes in five members of this family. Candidate rare variants were validated by Sanger sequencing in samples from 16 family members and 119 patients with sporadic IPF. The plasma levels of proteins encoded by the above candidate genes were also examined in 16 family members, 119 other patients with sporadic IPF and 120 age- and sex-matched healthy controls.

Results: In a Chinese Han family, MMP19 c.1222 C > T was identified in all familial IPF patients and six offspring from generations III and IV. This variant introduces a premature stop codon, which may damage protein function. Sanger sequencing revealed that 7.6% (9/119) of sporadic IPF patients harbored three MMP19 variants. The genetic risk analysis for pulmonary fibrosis showed that MMP19 c.1499 C > T and c.1316G > A were significantly associated with an increased risk of IPF (OR 3.66, p = 0.028 and OR 8.64, p < 0.001, respectively). The plasma levels of MMP19 were significantly higher in patients with sporadic or familial IPF than in healthy controls (all p < 0.001).

Conclusions: MMP19 variants were identified in familial or sporadic IPF, thus providing a potential new clue into IPF pathogenesis.

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来源期刊
Lung
Lung 医学-呼吸系统
CiteScore
9.10
自引率
10.00%
发文量
95
审稿时长
6-12 weeks
期刊介绍: Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.
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