热休克蛋白40（HSP40）共伴侣蛋白中的基因变异可调节缺血性心脏病风险。

Genetic variants in HSP40 co-chaperones modulate ischemic heart disease risk.

作者信息

Polshvedkina Olga, Kobzeva Ksenia, Bushueva Olga

机构信息

Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, 305041, Russia.

Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, 305041, Russia.

出版信息

Mol Biol Rep. 2025 Sep 10;52(1):889. doi: 10.1007/s11033-025-11014-z.

DOI:10.1007/s11033-025-11014-z

PMID:40928562

Abstract

BACKGROUND

The chaperoning system, which is responsible for protein homeostasis, plays a significant role in cardiovascular diseases. Among molecular chaperones or heat shock proteins (HSPs), the HSP40 family, the main co-chaperone of HSP70, remains largely underexplored, especially in ischemic heart disease (IHD) risk.

MATERIALS AND RESULTS

We genotyped 834 IHD patients and 1,328 healthy controls for three SNPs (rs2034598 and rs7189628 DNAJA2 and rs4926222 DNAJB1) using probe-based real-time PCR. We observed that SNP rs7189628 DNAJA2 was associated with increased IHD risk in smokers (effect allele [EA] T, OR = 1.65, 95%CI 1.01-2.71, p = 0.036), while SNP rs2034598 DNAJA2 was associated with increased IHD risk in non-smokers (EA A, OR = 1.22, 95%CI 1.02-1.47, p = 0.036). Oppositely, SNP rs4926222 DNAJB1 was associated with reduced IHD risk in patients under 62 years old (EA G, OR = 0.73, 95%CI 0.54-0.98, p = 0.02). These SNPs also modulated clinical parameters: rs7189628 was associated with higher platelet counts in the entire group (p = 0.03) and males (p = 0.02), while rs2034598 was associated with lower platelet counts in the same groups accordingly (p = 0.03 and p = 0.047), earlier IHD onset in males (p = 0.03), and reduced activated partial thromboplastin time in smokers (p = 0.01); rs4926222 DNAJB1 was Linked to elevated prothrombin index in patients aged 62 and higher (p = 0.04) and lower BMI in smokers (p = 0.005) and males (p = 0.02).

CONCLUSION

Our findings suggest that genetic variants in the HSP40 family influence IHD risk and clinical features in a context-specific manner.

摘要

背景

负责蛋白质稳态的伴侣系统在心血管疾病中起重要作用。在分子伴侣或热休克蛋白（HSPs）中，HSP40家族作为HSP70的主要共伴侣，在很大程度上仍未得到充分研究，尤其是在缺血性心脏病（IHD）风险方面。

材料与结果

我们使用基于探针的实时PCR对834例IHD患者和1328例健康对照者的三个单核苷酸多态性（SNP）（rs2034598和rs7189628位于DNAJA2基因，rs4926222位于DNAJB1基因）进行基因分型。我们观察到，SNP rs7189628位于DNAJA2基因与吸烟者IHD风险增加相关（效应等位基因 [EA] T，比值比 [OR] = 1.65，95%置信区间 [CI] 1.01 - 2.71，p = 0.036），而SNP rs2034598位于DNAJA2基因与非吸烟者IHD风险增加相关（EA A，OR = 1.22，95%CI 1.02 - 1.47，p = 0.036）。相反，SNP rs4926222位于DNAJB1基因与62岁以下患者IHD风险降低相关（EA G，OR = 0.73，95%CI 0.54 - 0.98，p = 0.02）。这些SNP还调节临床参数：rs7189628与整个组（p = 0.03）和男性（p = 0.02）的血小板计数较高相关，而rs2034598相应地与相同组中的血小板计数较低相关（p = 0.03和p = 0.047），男性IHD发病较早（p = 0.03），吸烟者活化部分凝血活酶时间缩短（p = 0.01）；rs4926222位于DNAJB1基因与62岁及以上患者的凝血酶原指数升高相关（p = 0.04），吸烟者（p = 0.005）和男性（p = 0.02）的体重指数较低相关。