Molecular Mechanism of Susceptibility Genes in Patients with Early-onset Hypertension Combined with Abnormal Potassium Metabolism Based on Whole Exome Sequencing
ZHANG Yu
GAO Ying
Shajidan·Abudureyimu
Dilihuma'er·Abulaiti
XING Zhi
Palida·Abulaiti
Abstract：Objective:To screen the susceptible genes of patients with early-onset hypertension combined with abnormal potassium metabolism based on whole-exome sequencing and bioinformatics analysis,and to explore the potential molecular mechanism.Methods:A total of 57 patients with early-onset hypertension were included.According to the blood potassium at the time of admission,the patients were divided into the normal potassium group(blood potassium 3.5-5.5 mmol/L,21 cases)and the low potassium group(blood potassium<3.5 mmol/L,36 cases).Peripheral blood samples were collected for whole exome sequencing and variant annotation,and the genes with interactive differences between the two groups were screened.Gene ontology(GO)functional enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed using the DAVID platform.The protein-protein interaction(PPI)network was constructed using the STRING database and imported into Cytoscape software for topological analysis to identify key node genes and functional modules.The protein expressions of plasma type Ⅳ collagen α3 chain(COL4A3)and type Ⅳ collagen α5 chain(COL4A5)in the two groups were detected by enzyme-linked immunosorbent assay(ELISA).Results:There were statistically differences in term of age,early diastolic rapid filling velocity of the left ventricle(E peak),the ratio of early diastolic rapid filling velocity of the left ventricle to late diastolic filling velocity of the left ventricle(A peak)(E/A),blood potassium and blood calcium levels,and the proportion of stroke/cerebral infarction between the two groups(P<0.05).A total of 63 interactive differential genes were identified through genetic screening.The PPI network topological analysis revealed that genes such as fibronectin 1(FN1),potassium voltage-gated channel subfamily Q member 1(KCNQ1),myosin(TTN),neurofibromatosis type 1(NF1),lysine methyltransferase 2D(KMT2D),insulin-like growth factor 2(IGF2),Barttin protein(BSND),calcium voltage-gated channel subfamily α1 H subunit(CACNA1H),sodium channel epithelial type 1 regulatory subunit γ(SCNN1G),COL4A3 and COL4A5 showed higher betweenness centrality(BC).The molecular complex detection(MCODE)clustering analysis revealed that FN1 and COL4A3,type Ⅳ collagen α4 chain(COL4A4),COL4A5,and type Ⅴcollagen α1 chain(COL5A1)formed a functional module of tight junction,which was significantly enriched in the integrin signaling pathway.The plasma levels of COL4A3 and COL4A5 in the low blood potassium group decreased more than those in the normal blood potassium group(P<0.05).Conclusion:Through exome sequencing and bioinformatics integration analysis,potential susceptibility genes of early-onset hypertension combined with abnormal potassium metabolism were screened out,including FN1,KMT2D,NF1,TTN,COL4A3,and COL4A5.COL4A3 and COL4A5 might be key molecules involved in the occurrence and development of the disease through the integrin signaling pathway.It might be theoretical basis of early-onset hypertension.
Keywords：early-onset hypertensionwhole exome sequencingbioinformatics analysistype Ⅳ collagen α3 chaintype Ⅳ collagen α5 chainmolecular mechanism
Publication Date：2026-03-25
Online Publishing Date：2026-04-07(First online date of this platform, not the publication date of the document)
Pages：8( 821-828 )