基于孟德尔随机化探究半乳糖凝集素8表达与支气管扩张症的因果关系

唐金铃; 郑少楚; 罗劲; 李尚; 徐阳; 孔晋亮

doi:10.16766/j.cnki.issn.1674-4152.004522

基于孟德尔随机化探究半乳糖凝集素8表达与支气管扩张症的因果关系

doi: 10.16766/j.cnki.issn.1674-4152.004522

广西医科大学第一附属医院呼吸与危重症医学科, 广西南宁 530000

基金项目:

国家自然科学基金项目 82560016

详细信息

通讯作者:
孔晋亮, E-mail: kjl071@126.com

中图分类号: R562.22
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出版历程
- 收稿日期: 2025-11-05
- 网络出版日期: 2026-11-10

Investigation of the causal relationship between LGALS8 expression and bronchiectasis based on Mendelian randomization

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530000, China

摘要

摘要: 目的本研究旨在通过孟德尔随机化(MR)分析和临床样本验证，探究半乳糖凝集素8(LGALS8)与支气管扩张症的因果关联。方法利用可用药基因的顺式表达数量性状位点(cis-eQTL)数据和蛋白质数量性状位点(pQTL)数据与支气管扩张数据进行孟德尔随机化(MR)分析。收集2021年7—10月广西医科大学第一附属医院临床确诊的34例非囊性支气管扩张患者及23例健康对照者的外周血样本，采用RT-qPCR验证其LGALS8表达水平，并分析在年龄、性别、BMI、吸烟状态、支气管扩张评估与分级指数(BACI)及E-FACED评分分组中的表达差异。结果 MR分析显示LGALS8基因表达与支气管扩张症风险增加有关(OR=1.122，95% CI：1.030~1.222，P=0.008)，LGALS8蛋白表达与支气管扩张症风险增加有关(OR=1.495，95% CI：1.161~1.924，P=0.002)，均不存在水平多效性和异质性。RT-qPCR结果显示，与对照组比较，支气管扩张组LGALS8的表达水平显著升高(P<0.001)，ROC曲线下面积为0.910(95% CI：0.808~0.995)。LGALS8表达在轻度E-FACED评分与中重度E-FACED评分之间差异有统计学意义(P=0.003)。结论 LGALS8表达与支气管扩张症存在因果关系，LGALS8在支气管扩张患者群体中表达升高，可能促进疾病的发生发展。
- 支气管扩张 /
- 半乳糖凝集素8 /
- 药物靶点 /
- 孟德尔随机化
Abstract: Objective To investigate the causal association between galectin-8 (LGALS8) and bronchiectasis using Mendelian randomization (MR) analysis and clinical sample validation. Methods MR analysis was performed using cis-expression quantitative trait locus (cis-eQTL) data of druggable genes, protein quantitative trait locus (pQTL) data, and bronchiectasis datasets. Peripheral blood samples were collected from 34 patients with non-cystic bronchiectasis and 23 healthy controls at the First Affiliated Hospital of Guangxi Medical University between July and October 2021. LGALS8 expression was measured by RT-qPCR and analyzed by age, sex, BMI, smoking status, bronchiectasis assessment of clinical impact (BACI) score, and E-FACED score. Results MR analysis showed that increased LGALS8 gene expression was associated with higher bronchiectasis risk (OR=1.122, 95% CI: 1.030-1.222, P=0.008), as was increased LGALS8 protein expression (OR=1.495, 95% CI: 1.161-1.924, P=0.002). No horizontal pleiotropy or heterogeneity was detected. RT-qPCR showed significantly elevated LGALS8 expression in patients than in controls (P<0.001), with an area under the receiver operating characteristic curve of 0.910 (95% CI: 0.808-0.995). LGALS8 expression also differed significantly between patients with mild and moderate-to-severe E-FACED scores (P=0.003). Conclusion LGALS8 expression was causally associated with bronchiectasis. LGALS8 expression is elevated in patients with bronchiectasis, potentially contributing to the onset and progression of the disease.
- Bronchiectasis /
- LGALS8 /
- Drug target /
- Mendelian randomization

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图 1 LGALS8预测支气管扩张的ROC曲线

Figure 1. The ROC curve of LGALS8 for predicting bronchiectasis

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表 1 支气管扩张症患者与健康受试者基线特征比较(例)

Table 1. Baseline characteristics of patients with bronchiectasis and healthy controls (cases)

组别	例数	年龄(岁)		性别		BMI			吸烟状态		E-FACED		支气管扩张评估与分级指数
组别	例数	< 60	≥ 60	男性	女性	< 18.5	18.5~24.0	>24.0	曾吸烟者	从未	轻度	中重度	低风险	中高危
支气管扩张患者	34	23	11	7	27	8	22	4	6	28	23	11	26	8
健康者	23	15	8	7	16	2	16	5	3	20
统计量		0.036^a		0.718^a		1.581^b			0.010^a
P值		0.849		0.397		0.114			0.922
注：^a为χ²值，^b为Z值。

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表 2 LGALS8基因表达与支气管扩张MR分析结果

Table 2. Mendelian randomization analysis results of LGALS8 gene expression in bronchiectasis

方法	nSNP	P值	OR值	95% CI
MR Egger	16	0.034	1.161	1.025~1.315
Weighted median	16	0.043	1.126	1.004~1.263
Inverse variance weighted	16	0.008	1.122	1.030~1.222
Simple mode	16	0.127	1.158	0.969~1.383
Weighted mode	16	0.079	1.128	0.995~1.280

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表 3 LGALS8蛋白表达与支气管扩张MR分析结果

Table 3. Mendelian randomization analysis results of LGALS8 protein expression in bronchiectasis

方法	nSNP	P值	OR值	95% CI
MR Egger	7	0.077	1.627	1.060~2.500
Weighted median	7	0.004	1.501	1.142~1.974
Inverse variance weighted	7	0.002	1.495	1.161~1.924
Simple mode	7	0.268	1.398	0.817~2.392
Weighted mode	7	0.036	1.506	1.117~2.032

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表 4 不同临床特征分组间支气管扩张患者LGALS8表达水平比较

Table 4. Comparison of LGALS8 expression levels in different clinical characteristic subgroup of bronchiectasis patients

项目	例数	LGALS8相对表达水平 [M(P₂₅, P₇₅)]	统计量	P值
年龄			124.000^a	0.942
<60岁	23	2.774(2.058, 4.290)
≥60岁	11	2.897(1.636, 7.070)
性别			64.000^a	0.206
女性	27	2.754(1.698, 4.290)
男性	7	3.044(2.324, 4.581)
BMI			0.158^b	0.924
<18.5	8	2.764(1.839, 4.330)
18.5~24.0	22	2.836(1.897, 5.172)
>24.0	4	2.551(1.686, 5.152)
吸烟状态			57.000^a	0.238
从不吸烟	28	2.764(1.721, 4.022)
曾经吸烟	6	3.792(2.258, 5.594)
BACI风险分级			102.000^a	0.952
低风险	26	2.836(1.897, 4.392)
中高风险	8	2.764(1.845, 4.197)
E-FACED分级			49.000^a	0.003
轻度	23	2.324(1.636, 3.013)
中重度	11	4.581(2.545, 8.631)
注：^a为U值，^b为H值。

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