Association of Rs2071410 on Furin with Transient Ischemic Attack Susceptibility and Prognosis in a Chinese Population

Sun, Qin-Xiang; Zhou, Haimei; Du, Qianqian

doi:10.12659/msm.897122

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…An elevated expression of furin in adipose tissue from obese mice compared with the lean controls found by an animal study14 further support this hypothesis. Moreover, the FURIN gene polymorphisms have been associated with abdominal obesity15 and associated metabolic disorders, for example, metabolic syndrome (MetS),16 hypertension,17 coronary artery disease18–20 and stroke21 in populations.…”

Section: Introductionmentioning

confidence: 99%

Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults

Ren

Zhang²,

Zhang

et al. 2020

Postgraduate Medical Journal

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BackgroundAs a key enzyme of natriuretic peptides system playing an integral role in energy homeostasis, furin may be a potential contributor to obesity. However, the association between furin and obesity has been scarcely studied. This study aims to examine the prospective association between serum furin and abdominal obesity.MethodsWaist circumference (WC) was measured twice 4 years apart for a total of 892 Chinese adults free of abdominal obesity at baseline. Abdominal obesity was defined as WC over 85 cm for men and as WC over 80 cm for women. A Cox proportional hazard model was constructed to examine the association of baseline serum furin with incident abdominal obesity.ResultsAfter an average 4 years of follow-up, 184 participants developed new abdominal obesity. Baseline serum furin was significantly associated with dynamic body weight during follow-up (β=−0.593, p=0.003). Participants with a higher level of serum furin at baseline were less likely to develop new abdominal obesity compared with those with a lower level of serum furin (HR=0.81, 95% CI 0.67 to 0.97).ConclusionsA lower level of serum furin predicts a higher risk of developing future abdominal obesity in Chinese adults. Furin deficiency may be a contributor to abdominal obesity but still needs further investigations.

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Section: Introductionmentioning

confidence: 99%

Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults

Ren

Zhang²,

Zhang

et al. 2020

Postgraduate Medical Journal

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“…The NP family includes 3 well-characterized hormones—atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP), 16 and the related protease convertases (furin and corin). 17,18 Sequence variants in their coding genes, e.g., NPPA (the gene coding ANP), 19,20 NPPB (the gene coding BNP), 21 CORIN (the gene coding corin), 22,23 and FURIN (the gene coding furin) 24,25 but not NPPC (the gene coding CNP), have previously been related to susceptibility to IS and its main risk factors, e.g., hypertension and atherosclerosis. Although these studies highlight the contributions of genetic variants in the NP system to the risks of IS, additional underlying molecular mechanisms remain to be elucidated.…”

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confidence: 99%

DNA Methylation of the Natriuretic Peptide System Genes and Ischemic Stroke

Peng

Fan

et al. 2022

Neurol Genet

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Background and ObjectivesThe natriuretic peptide (NP) system has been considered an important regulator for ischemic stroke (IS) with a limited clinical implication. A better understanding of the underlying molecular mechanisms is urgent. Here, we aimed to examine the role of DNA methylation of NP system genes in IS.MethodsDNA methylation at promoter regions of 4 core NP system genes, e.g., CORIN, FURIN, NPPA, and NPPB, was measured by targeted bisulfite sequencing in 853 patients with IS and 918 controls. We first examined the association between DNA methylation at each single CpG and IS, followed by gene-based and gene set analyses to examine the joint associations of DNA methylation at multiple CpGs in a gene or all 4 genes as a pathway with IS.ResultsAfter control of covariates and multiple testing, DNA methylation at 19 of the 36 assayed CpGs was individually associated with IS at q < 0.05. Higher average methylation levels at the targeted regions of CORIN (odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.56–0.73), FURIN (OR = 0.78, 95% CI: 0.69–0.88), and NPPA (OR = 0.78, 95% CI: 0.69–0.88) were associated with a lower odds of IS (all q < 0.05). The truncated product method revealed the same gene-based associations (all q < 0.05) and found that DNA methylation at all 4 NP system genes together was jointly associated with IS (p = 0.0001).DiscussionDNA methylation at NP system genes was downregulated in patients with IS. Our results may unravel a molecular mechanism underlying the regulating effect of the NP system on IS and highlight the relevance of testing the joint effect of multiple CpGs in the epigenetic analysis.

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“…130 A genetic study reported that the CG/ GG genotypes of the FURIN rs2071410 SNP are associated with ∼50% increased risk of transient ischemic attack (TIA), compared with the homozygous CC genotype (Table 2). 95 This SNP potentially contributes to a reduction in furin activity and an increase in hypertension, 35 a strong associated risk factor of TIA. 131 In stroke, however, GWAS meta-analyses have revealed that FURIN is one of the putative causal genes.…”

Section: ■ Ischemic Strokementioning

confidence: 99%

Functional Roles of Furin in Cardio-Cerebrovascular Diseases

Wichaiyo,

Koonyosying,

Morales

2024

ACS Pharmacol. Transl. Sci.

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Furin plays a major role in post-translational modification of several biomolecules, including endogenous hormones, growth factors, and cytokines. Recent reports have demonstrated the association of furin and cardio-cerebrovascular diseases (CVDs) in humans. This review describes the possible pathogenic contribution of furin and its substrates in CVDs. Early-stage hypertension and diabetes mellitus show a negative correlation with furin. A reduction in furin might promote hypertension by decreasing maturation of B-type natriuretic peptide (BNP) or by decreasing shedding of membrane (pro)renin receptor (PRR), which facilitates activation of the renin−angiotensin−aldosterone system (RAAS). In diabetes, furin downregulation potentially leads to insulin resistance by reducing maturation of the insulin receptor. In contrast, the progression of other CVDs is associated with an increase in furin, including dyslipidemia, atherosclerosis, ischemic stroke, myocardial infarction (MI), and heart failure. Upregulation of furin might promote maturation of membrane type 1-matrix metalloproteinase (MT1-MMP), which cleaves low-density lipoprotein receptor (LDLR), contributing to dyslipidemia. In atherosclerosis, elevated levels of furin possibly enhance maturation of several substrates related to inflammation, cell proliferation, and extracellular matrix (ECM) deposition and degradation. Neuronal cell death following ischemic stroke has also been shown to involve furin substrates (e.g., MT1-MMP, hepcidin, and hemojuvelin). Moreover, furin and its substrates, including tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1), are capable of mediating inflammation, hypertrophy, and fibrosis in MI and heart failure. Taken together, this evidence provides functional significance of furin in CVDs and might suggest a potential novel therapeutic modality for the management of CVDs.

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Association of Rs2071410 on Furin with Transient Ischemic Attack Susceptibility and Prognosis in a Chinese Population

Cited by 6 publications

References 36 publications

Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults

Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults

DNA Methylation of the Natriuretic Peptide System Genes and Ischemic Stroke

Functional Roles of Furin in Cardio-Cerebrovascular Diseases

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