rs13063138介导的溶酶体钾离子通道TMEM175在帕金森病中的调控作用

王子豪; 夏欢; 姚亚妮; 雍雨暄; 李沛珊; 商书盈; 杨新玲

doi:10.16766/j.cnki.issn.1674-4152.004402

rs13063138介导的溶酶体钾离子通道TMEM175在帕金森病中的调控作用

doi: 10.16766/j.cnki.issn.1674-4152.004402

1.
新疆医科大学第二附属医院重点实验室，新疆乌鲁木齐 830000
2.
新疆医科大学附属肿瘤医院核医学科，新疆乌鲁木齐 830011
3.
新疆医科大学第一附属医院神经内科，新疆乌鲁木齐 830000

基金项目:

国家自然科学基金项目 82371258

新疆维吾尔自治区重点研发计划项目 2023B03003

天山英才-科技创新领军人才项目 2022TSYCLJ0066

详细信息

通讯作者:
杨新玲，E-mail：yangxinling2014@163.com

中图分类号: R745
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- 被引次数: 0
出版历程
- 收稿日期: 2025-06-13
- 网络出版日期: 2026-06-02

Regulatory role of lysosomal potassium channel TMEM175 mediated by rs13063138 in Parkinson's disease

1.
Key Laboratory, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, China

摘要

摘要: 目的探讨TMEM175基因表达水平及其遗传位点与帕金森病(PD)风险之间的潜在关联。方法本研究于2023年6月—2024年9月在新疆医科大学第二附属医院开展，共纳入215名参与者(105名PD患者，110名健康对照)，通过酶联免疫吸附试验(ELISA)检测血清TMEM175表达水平，结合全基因组关联研究(GWAS)数据开展遗传组学及共定位分析，并利用单细胞RNA测序与染色质可及性分析探索TMEM175在脑细胞中的表达情况。结果 PD患者组TMEM175表达水平为(183.27±11.97)ng/mL，显著低于健康对照组的(187.28±10.24)ng/mL(t=2.647, P=0.009)。Logistic回归分析显示，TMEM175水平升高显著降低PD发生风险，尤其在浓度较高的Q3(185.32~＜192.92 ng/mL)和Q4(＞192.92 ng/mL)组中具有统计学意义(P＜0.05)。遗传组学分析表明TMEM175对PD具有保护作用(OR=0.75，95% CI：0.55~1.01，P=0.048)，关键共定位位点rs13063138可能通过调控TMEM175影响PD发生风险。单细胞RNA测序数据显示，TMEM175在星形胶质细胞和少突胶质细胞中高表达，提示其在胶质细胞功能中具有重要作用。结论本研究从血清水平、遗传背景及细胞功能3个层面揭示了TMEM175在PD中的作用，提供了TMEM175作为PD潜在治疗靶点的证据。
- 帕金森病 /
- TMEM175 /
- 遗传组学 /
- 单细胞测序 /
- 共定位分析
Abstract: Objective To explore the potential association between TMEM175 gene expression levels, its genetic loci, and the risk of Parkinson's disease (PD). Methods This study was conducted from June 2023 to September 2024 at the Second Affiliated Hospital of Xinjiang Medical University. A total of 215 participants (105 patients with PD and 110 healthy controls) were included in the study. Serum TMEM175 expression levels were measured using enzyme-linked immunosorbent assay (ELISA). Genomic studies, including a genome-wide association study (GWAS) and colocalization analysis, were conducted. Single-cell RNA sequencing and chromatin accessibility analyses were employed to explore the expression characteristics of TMEM175 in brain cells. Results The expression level of TMEM175 in the PD patient group [(183.27±11.97) ng/mL] was significantly lower than that in the healthy control group [(187.28±10.24) ng/mL], with a statistically significant difference (t=2.647, P=0.009). Logistic regression analysis showed that increased TMEM175 levels significantly reduced the risk of PD, particularly in the higher concentration Q3 (185.32-＜192.92 ng/mL) and Q4 (> 192.92 ng/mL) groups, which showed statistical significance (P < 0.05). Genomic analysis indicated that TMEM175 has a protective effect on PD (OR=0.75, 95% CI: 0.55-1.01, P=0.048), and the key co-localized locus rs13063138 may influence PD risk by regulating TMEM175. Single-cell RNA sequencing data showed that TMEM175 is highly expressed in astrocytes and oligodendrocytes, suggesting its important role in glial cell function. Conclusion This study reveals the role of TMEM175 in PD from three perspectives: serum levels, genetic background, and cellular function. It provides evidence supporting TMEM175 as a potential therapeutic target for PD.
- Parkinson's disease /
- TMEM175 /
- Genomics /
- Single-cell sequencing /
- Colocalization analysis

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图 1 遗传组学分析

注：A为TMEM175与PD风险的散点图；B为TMEM175与PD风险的共定位分析。

Figure 1. Genomic analysis

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图 2 TMEM175的表达特征分析

Figure 2. Expression profiling analysis of TMEM175

下载: 全尺寸图片幻灯片

表 1 2组研究对象基线资料比较

Table 1. Comparison of baseline characteristics between the two groups

项目	总体(n=215)	健康对照组(n=110)	帕金森病组(n=105)	统计量	P值
性别[例(%)]				0.336^a	0.563
女性	120(55.8)	64(58.2)	56(53.3)
男性	95(44.2)	46(41.8)	49(46.7)
TMEM175(x±s，ng/mL)	185.32±11.27	187.28±10.24	183.27±11.97	2.647^b	0.009
年龄(x±s，岁)	66.11±9.57	65.56±9.81	66.69±9.32	0.859^b	0.391
BMI(x±s)	24.82±4.29	24.61±5.00	25.04±3.40	0.732^b	0.465
高血压[例(%)]	115(53.5)	64(58.2)	51(48.6)	1.631^a	0.202
糖尿病[例(%)]	60(27.9)	23(20.9)	37(35.2)	4.773^a	0.029
心力衰竭[例(%)]	14(6.5)	1(0.9)	13(12.4)	9.876^a	0.002
冠心病[例(%)]	36(16.7)	15(13.6)	21(20.0)	1.136^a	0.286
心绞痛[例(%)]	19(8.8)	7(6.4)	12(11.4)	1.136^a	0.286
中风[例(%)]	57(26.5)	29(26.4)	28(26.7)	0.050^a	0.859
癌症[例(%)]	12(5.6)	3(2.7)	9(8.6)	2.468^a	0.117
注：^a为χ²值，^b为t值。

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表 2 TMEM175与PD风险关系的logistic回归分析

Table 2. Logistic regression analysis of the relationship between TMEM175 and PD risk

TMEM175	模型1		模型2		模型3
TMEM175	OR(95% CI)	P值	OR(95% CI)	P值	OR (95% CI)	P值
Q2	0.59(0.27~1.27)	0.178	0.50(0.23~1.11)	0.091	0.48(0.20~1.16)	0.104
Q3	0.42(0.19~0.91)	0.029	0.44(0.19~0.98)	0.046	0.29(0.12~0.68)	＜0.001
Q4	0.40(0.19~0.88)	0.023	0.36(0.16~0.81)	0.014	0.30(0.12~0.72)	＜0.001
注：模型1为未调整协变量；模型2调整了性别和年龄；模型3进一步调整了高血压、糖尿病、癌症、心力衰竭、冠状动脉疾病、中风、心绞痛及BMI。

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