Nucleosides, Nucleotides & Nucleic Acids最新文献

{"title":"DNA nanotechnology for cell-free DNA marker for tumor detection: a comprehensive overview.","authors":"Sara Sami Soliman, Fathi E Abd El-Samie, Saied M Abd El-Atty, Wael Badawy, Abeer Eshra","doi":"10.1080/15257770.2024.2337853","DOIUrl":"10.1080/15257770.2024.2337853","url":null,"abstract":"<p><p>Advancements in DNA nanotechnology have led to new exciting ways to detect cell-free tumor biomarkers, revolutionizing cancer diagnostics. This article comprehensively reviews recent developments in this field, discussing the significance of liquid biopsies and DNA nanomachines in early cancer detection. The accuracy of cancer diagnosis at its early stages is expected to be significantly improved by identifying biomarkers. Liquid biopsies, offering minimally-invasive testing, hold the potential for capturing tumor-specific components like circulating tumor cells, cell-free DNA, and exosomes. DNA nanomachines are advanced molecular devices that exploit the programmability of DNA sequences for the ultrasensitive and specific detection of these markers. DNA nanomachines, nanostructures made of DNA that can be designable and switchable nanostructures, have a wide range of advantages for detecting tumor biomarkers, including non-invasiveness, affordability, high sensitivity, and specificity. Scientists also work on dealing with challenges like low marker concentrations and interference, which are addressed through microfluidic integration, nanomaterial amplification, and indirect signal detection. Despite advances, multiplex detection remains a challenge. In conclusion, DNA nanomachines bear immense promise for cancer diagnostics, advocating personalized treatment and improving patient outcomes. Continued research could redefine how we find and treat tumors, leading to better patient outcomes.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"276-290"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of human epididymis protein 4 on hyperoxia-induced bronchial dysplasia in newborn rats.","authors":"Xiaofang Yan, Xing Feng, Yan Gao, Dawei Liu, Lin Bai, Lu Xu","doi":"10.1080/15257770.2024.2356208","DOIUrl":"10.1080/15257770.2024.2356208","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to elucidate the role and the underlying mechanism of human epididymis protein 4 (HE4) in the pathogenesis of hyperoxia-induced bronchial dysplasia in newborn rats.</p><p><strong>Methods: </strong>Forty neonatal Sprague-Dawley (SD) rats were separated into two groups: a normal control group (20.8% oxygen concentration) and a hyperoxia-induced group (85% oxygen concentration). Three time intervals of 24 h, 3 days and 7 days were chosen for each group. Haematoxylin-eosin staining was used to identify the pathological alterations in the lung tissue of the SD rats. Enzyme-linked immunosorbent assay was used to evaluate plasma protein levels. Real-time reverse transcription polymerase chain reaction was used to determine messenger RNA (mRNA) expression.</p><p><strong>Results: </strong>In newborn SD rats, hyperoxia intervention within 7 days may result in acute lung damage. In the plasma and tissue of newborn SD rats, hyperoxia induction may raise levels of HE4, matrix metalloproteinases (MMP) 9 and tissue inhibitors of metalloproteinases (TIMP) 1. We discovered that the HE4 protein activates the phosphorylation of extracellular regulated protein kinases (ERK) and p65, activates the downstream MMP9 signalling pathway, inhibits MMP9 mRNA expression, inhibits protein activity, reduces type I collagen degradation, increases collagen secretion and promotes matrix remodelling and fibrosis in neonatal rat primary alveolar type II epithelial cells by overexpressing and silencing the HE4 gene.</p><p><strong>Conclusion: </strong>Through the ERK, MMP9 and TIMP1 signalling pathways, HE4 mediates the pathophysiological process of hyperoxia-induced lung damage in rats. Lung damage and lung basal remodelling are mediated by HE4 overexpression.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"378-396"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of FKBP12 on dextran sulfate sodium-induced ulcerative colitis in mice as a tacrolimus receptor.","authors":"Birong Wang, Tingzan Li, Liqin Xu, Yuxi Cai","doi":"10.1080/15257770.2024.2320817","DOIUrl":"10.1080/15257770.2024.2320817","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a multifactorial intestinal disease with a high incidence. In recent years, there has been an urgent need for pleiotropic drugs with a clear biosafety profile. Tacrolimus (TAC) is an immunosuppressant with stronger <i>in vivo</i> effects and better gastrointestinal absorption and is considered a potential treatment for UC. FKBP12 is a mediator of TAC immunosuppression; however, it is unclear whether it can participate in the development of UC in combination with TAC. The purpose of this study is to preliminarily validate the function of FKBP12 by establishing dextran sulfate sodium (DSS)-induced UC model and TAC treatment. The results revealed that TAC was effective in alleviating DSS-induced UC symptoms such as body weight and disease activity index (DAI). TAC significantly protects colonic tissue and attenuates DSS-induced histomorphological changes. In addition, FKBP12 is down-regulated in the intestinal tissue of DSS-induced UC mice and in serum samples of UC patients. In conclusion, our study revealed that FKBP12 may act as a TAC receptor to have anti-inflammatory and protective effects on DSS-induced UC in mice, which will provide a new option for the treatment of UC.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"206-221"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deprotection of N1-methyladenosine-containing RNA using triethylamine hydrogen fluoride.","authors":"A Apostle, S Fang","doi":"10.1080/15257770.2024.2353181","DOIUrl":"10.1080/15257770.2024.2353181","url":null,"abstract":"<p><p>The <i>N</i>¹-methyladenosine (m¹A) epigenetic modification exists in many RNAs and is related to many human diseases. Chemically synthesized RNAs containing the modification are required for projects aimed at studying biological processes, mechanisms, and pathogenesis related to m¹A. Existing methods for the synthesis of m¹A containing RNAs use tetrabutylammonium fluoride (TBAF) for the deprotection of the 2'-silyl protecting groups. Since TBAF is nonvolatile, and is relatively non-polar, its use in the desilylation of RNA requires repeated desalting, which is tedious and gives low yields. Here we report the use of the volatile and neat triethylamine hydrogen fluoride (TEA-HF) for desilylation of m¹A RNA synthesis. We found that the method is much simpler, and-in our hands-give significantly higher yield of RNA. Two major concerns for m¹A RNA synthesis are depurination and Dimroth rearrangement. HPLC and MALDI MS of the RNA indicated that depurination is not a problem for the new method. The absence of Dimroth rearrangement is proven by RNA digestion followed by HPLC analysis of the nucleosides.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"318-325"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between polymorphism at codon 469 of the ICAM-1 gene and Henoch-Schönlein purpura in an Iranian cohort.","authors":"Shima Salehi, Amir Hozhabrpour, Somayeh Takrim Nojehdeh, Marzieh Mojbafan","doi":"10.1080/15257770.2024.2334360","DOIUrl":"10.1080/15257770.2024.2334360","url":null,"abstract":"<p><p>Henoch-Schönlein purpura (HSP) is a common form of IgA1-mediated blood vessel inflammation affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been shown to be associated with HSP in different populations; in this study, we investigated its potential association and influence on the development of severe complications in Iranian HSP patients. Twenty-three patients diagnosed with IgAV/HSP according to the criteria of the American College of Rheumatology (ACR) with 53 age- and sex-matched control subjects were referred to us. Cases and controls were genotyped using Sanger sequencing. Based on our research data, we found an association between codon 469 K/E of the <i>ICAM1</i> gene and risk of HSP. Our results revealed that KK genotype and allele K are more common in control than in the HSP group, therefore the subjects with KK genotype are protected against HSP. Our data also suggested that the genotype EE is associated with higher risk of HSP progression compared to KK genotype.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"259-266"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics analysis of ferroptosis-related gene signature in inflammation and immunity in intervertebral disc degeneration.","authors":"Wei Liu, Hui-Min Li, Guangchao Bai","doi":"10.1080/15257770.2024.2332403","DOIUrl":"10.1080/15257770.2024.2332403","url":null,"abstract":"<p><p>Ferroptosis has recently been shown to play a significant role in the progression of intervertebral disk degeneration (IDD), although the underlying mechanism is still unknown. The objective of this work was to use stringent bioinformatic techniques to clarify the crucial roles played by genes associated with ferroptosis in the emergence of IDD. For additional study, the microarray data pertinent to the IDD were acquired from the Gene Expression Omnibus database. The ferroptosis-related and IDD-related genes (FIDDRGs) were identified using a variety of bioinformatic techniques, which were also used to carry out function enrichment analysis, protein-protein correlation analysis, build the correlation regulatory network, and examine the potential connections between ferroptosis and immune abnormalities and inflammatory responses in IDD. A total of 16 FIDDRGs were eliminated for the further function enrichment analysis, and 10 hub FIDDRGs were chosen to build the correlation regulatory network. Hub FIDDRGs were shown to be highly associated with M2 macrophages and hub inflammatory response-related genes in IDD. When seen as a whole, our findings can give fresh perspectives on the mechanistic studies of ferroptosis in the emergence of IDD and new prospective targets for the therapeutic approaches.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"238-258"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-138 inhibits hypoxia-inducible factor 1α expression in breast cancer cells.","authors":"Mohammad Fayyad-Kazan, Rim ElDirani, Michella Ghassibe-Sabbagh, Eva Hamade, Nader Hadifeh, Rania El Majzoub, Hussein Fayyad-Kazan, Bassam Badran","doi":"10.1080/15257770.2024.2351134","DOIUrl":"10.1080/15257770.2024.2351134","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia, a critical feature during cancer development, leads to the stabilization and activation of the hypoxia-inducible factor 1-alpha (HIF-1α) to drive the expression of many target genes which in turn can promote many aspects of breast cancer biology, mainly metastasis and resistance to therapy. MicroRNAs are known to modulate the expression of many genes involved in breast cancer tumorigenesis. In this study, we examined the regulatory effect of miRNAs on HIF1α expression.</p><p><strong>Methods: </strong>MCF-7 and MDA-MB-231 were cultivated under normoxia or hypoxia conditions. TaqMan-Low Density Array (TLDA) was used to characterize the miRNA signatures. Wild-Type (WT) or mutated fragments of HIF-1α 3'UTR containing the miR-138 potential target site were cloned downstream of the Renilla luciferase gene in the psiCHECK-1 plasmid. Luciferase assays were then carried out. A lentiviral vector containing copGFP as a reporter gene was prepared and transduced into MCF-7 and MDA-MB-231 cells to assess the effect of identified deregulated miRNAs on HIF-1α expression.</p><p><strong>Results: </strong>Under hypoxic conditions, MCF-7 cells showed deregulated expression for 12 miRNAs. In the case of MDA-MB-231 cells, 16 miRNAs were deregulated in response to hypoxia. Interestingly, miR-138 that was downregulated in both MCF-7 and MDA-MB-231 cells cultivated under hypoxic conditions appeared to have a binding site in 3'UTR of HIF-1α. Moreover, our results indicated that miR-138 could down regulate HIF-1α expression, upon binding directly to its 3'UTR.</p><p><strong>Conclusions: </strong>Interestingly, our data highlights miR-138 as a potential therapeutic target to reduce HIF-1α expression and subsequently restrain breast cancer invasion and metastasis.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"302-317"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of the <i>MBL2</i> gene rs1800450 variant on COVID-19 development in Turkish patients.","authors":"Mustafa Capraz, Akin Tekcan, Mustafa Cihangiroglu, Ayse Feyda Nursal, Aylin Capraz, Elif Menekse, Hatice Dortok Demir, Nilufer Kuruca, Serbulent Yigit","doi":"10.1080/15257770.2024.2395872","DOIUrl":"10.1080/15257770.2024.2395872","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) is a recent pandemic occurring worldwide due to the <i>severe acute respiratory syndrome coronavirus 2</i> (SARS-CoV-2) virus, spreading mainly through large respiratory droplets or maybe through other transmission routes. The human genome has the most varied immune response genes correlated with infectious diseases. Genetic variants of mannose-binding lectin 2 (<i>MBL2</i>), an immunomodulatory gene, were associated with the risk, severity, and frequency of viral infections. In the present study, we hypothesized that the <i>MBL2</i> gene rs1800450 variant could be associated with the development of COVID-19 disease in a Turkish population. Ninety-eight COVID-19 patients and 98 healthy, ethnically matched controls were studied. We isolated genomic DNA from whole blood and analyzed the <i>MBL2</i> rs1800450 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Associations were analyzed with the SPSS 20 statistical software. We found that <i>MBL2</i> rs1800450 genotype distribution was significantly different between patients and controls. The patients had a higher <i>MBL2</i> rs1800450 AA genotype than the controls had (4.94% in patients vs. 3.12% in controls, <i>p</i> = 0.006). The subjects carrying AA genotype had a 10.83-fold increased risk for COVID-19 disease (OR = 10.83, %95 CI = 1.359-86.349). We could not detect any significant difference between the COVID-19 patients and healthy controls in allele frequencies. Our findings demonstrated that the <i>MBL2</i> rs1800450 BB genotype might increase the susceptibility to COVID-19 disease in the Turkish population. We suggest further studies with a larger sample size and other ethnic populations.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"79-89"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between <i>ACE</i> (rs4343 and rs1799752), <i>AGTR1</i> (rs5186), and <i>PAI-1</i> (rs2227631) polymorphisms in the host and the severity of Covid-19 infection.","authors":"Seher Polat, Zühal Özer Şimşek","doi":"10.1080/15257770.2024.2387033","DOIUrl":"10.1080/15257770.2024.2387033","url":null,"abstract":"<p><strong>Objective: </strong>It is necessary to identify appropriate clinical, biochemical, epidemiological and genetic biomarkers to elucidate the underlying mechanisms of the coronavirus disease-2019 (COVID-19) disease. The study focused on not only the link between disease severity (non-intense unit care (non-ICU) versus intensive unit care (ICU) and genetic susceptibility in COVID-19 patients but also the connection between comorbidity and genetic susceptibility affecting the severity of COVID-19.</p><p><strong>Subject and methods: </strong>One hundred and sixty-two COVID-19 patients treated in the non-ICU and ICU in Kayseri City Hospital were included. All volunteers underwent a physical examination and biochemical evaluation. Angiotensin-converting enzyme (<i>ACE</i> p.T776T G > A(rs4343) and g.16471_16472delinsALU (also referred to as I/D polymorphism; rs1799752), angiotensin II receptor type-1 (<i>AGTR1)</i> c.*86A > C (also referred to as A1166C; rs5186), and plasminogen activator inhibitor-1 (<i>PAI-1</i>-844 G > A (rs2227631) polymorphisms were analysed as well.</p><p><strong>Results: </strong>To have ACE \"ID\" genotype did not change the severity of the disease (OR: 0.92, 95% CI: 0.41-2.1, <i>p</i> = 0.84), but decreased the mortality risk 2.9-fold (OR: 2.9, 95% CI: 1.1-7.0, <i>p</i> = 0.03). In <i>PAI-1</i>-844 G > A, having the \"AA\" genotype in the \"A\" recessive model increased the risk of the diabetes mellitus (DM) 2.3-fold (OR: 2.3 95%, CI: 1.16-4.66, <i>p</i> = 0.018). In the \"G\" recessive model, to have the GG genotype increased the risk of chronic kidney disease (CKD) 4.8-fold (OR:4.8, 95% CI: 1.5-15.5, <i>p</i> = 0.008). \"GG\" genotype in the DM group had a higher fibrinogen level compared to those with the \"AG\" genotype (AG:4847.2 mg/L (1704.3) versus GG:6444.67 mg/L (1861.62) <i>p</i> = 0.019) and \"AA\" genotype in the CKD group had lower platelet levels and those with \"GG\" had higher platelet levels (AA:149 µL (18-159) versus GG: 228 µL (146-357) <i>p</i> = 0.022).</p><p><strong>Conclusion: </strong>This study was shown that genetic predispositions that causes comorbidities were also likely to affect the prognosis of COVID-19.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"57-78"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual effects of <i>PCSK9 E670G</i> (rs505151) variation in patients with in-stent restenosis: Variable effects on restenosis risk according to concomitant chronic conditions.","authors":"Gulcin Ozkara, Ezgi Irmak Aslan, Ayse Begum Ceviz, Gonca Candan, Fidan Malikova, Allison Pinar Eronat, Ozgur Selim Ser, Onur Kılıcarslan, Ozlem Kucukhuseyin, Cem Bostan, Ahmet Yildiz, Oguz Ozturk, Hulya Yilmaz-Aydogan","doi":"10.1080/15257770.2024.2316724","DOIUrl":"10.1080/15257770.2024.2316724","url":null,"abstract":"<p><p>Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function <i>E670G</i> (rs505151) mutation of the <i>PCSK9</i> gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the <i>E670G</i> variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of <i>PCSK9 E670G</i> (<i>p</i> < 0.05), hyperlipidemia (HL) (<i>p</i> < 0.001), and type 2 diabetes (T2DM) (<i>p</i> < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the <i>E670G</i>-G allele was associated with hypercholesterolemia and a higher risk of ISR (<i>p</i> < 0.001), while the <i>E670G-</i>AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels (<i>p</i> < 0.05) and the <i>E670G</i>-AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the <i>PCSK9 E670G</i> variation may be involved in the risk of ISR in association with concomitant metabolic diseases.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"185-205"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}