Human Gene最新文献_第10页

The relative copy number of mitochondrial DNA in peripheral blood as a prognostic marker for the development of polycystic ovarian syndrome in west Iraqi women 外周血中线粒体DNA的相对拷贝数作为西伊拉克妇女多囊卵巢综合征发展的预后标志物

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-30 DOI: 10.1016/j.humgen.2025.201442

Zaman N. Hameed , Rashied M. Rashied , Sawsan M. Kareem

Mitochondria are the primary producers of free radicals, particularly reactive oxygen species (ROS), so disruptions in mitochondrial activity at the cellular level may have an impact on overall metabolic balance, leading to the hypothesis that anomalies in mitochondrial metabolism markers may be associated with polycystic ovary syndrome (PCOS).We sought to assess mitochondrial DNA (mtDNA) copy number as an indication of mitochondrial malfunction induced by higher oxidative stress (OS) in women with PCOS, as well as, to study the independent relationship between mtDNA copy number and PCOS development. The case-control research comprised ninety women, sixty with PCOS and thirty healthy women as controls at reproductive age.

Our result revealed that women with PCOS had significantly lower mitochondrial DNA copy number compared to non-PCOS group (P = 0.000). In the PCOS group, reduce mtDNA copy number was adversely correlated with body mass index and insulin resistance indicators, Meantime, positively correlated with the quantitative insulin sensitivity check index (QUICKI) score. The Receiver operating characteristic curve (ROC) indicating the diagnostic value of mitochondrial copy number in the development of PCOS, with an area under the curve of 0.871 (0.759–0.984) at (p = 0.000) and sensitivity 89 % for parameter. Furthermore, we discovered that the relationship between PCOS and decreased mtDNA copy number is independent of other characteristics. In conclusion, according to above, reduce mtDNA copy number may be a risk factor in PCOS development in women.

线粒体是自由基，尤其是活性氧（ROS）的主要产生者，因此在细胞水平上线粒体活性的破坏可能会影响整体代谢平衡，从而导致线粒体代谢标志物异常可能与多囊卵巢综合征（PCOS）相关的假设。我们试图评估线粒体DNA （mtDNA）拷贝数作为PCOS女性较高氧化应激（OS）诱导的线粒体功能障碍的指标，并研究mtDNA拷贝数与PCOS发展之间的独立关系。病例对照研究包括90名妇女，60名多囊卵巢综合征患者和30名育龄健康妇女作为对照。我们的研究结果显示，与非PCOS组相比，PCOS女性的线粒体DNA拷贝数显著降低（P = 0.000）。PCOS组mtDNA拷贝数减少与体重指数、胰岛素抵抗指标呈负相关，与胰岛素敏感性定量检查指数（QUICKI）评分呈正相关。受试者工作特征曲线（ROC）显示线粒体拷贝数在PCOS发展中的诊断价值，曲线下面积为0.871 (0.759-0.984)(p = 0.000)，参数敏感性为89%。此外，我们发现PCOS与mtDNA拷贝数减少之间的关系是独立于其他特征的。综上所述，mtDNA拷贝数减少可能是女性PCOS发生的危险因素。

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引用次数: 0

Distinguishing between founder and host population mtDNA lineages in the Ashkenazi population 在德系犹太人群体中区分创始人群和寄主人群的mtDNA谱系

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-28 DOI: 10.1016/j.humgen.2025.201445

Joseph Livni , Karl Skorecki

The size of the founding generation of founder populations is typically small. For example, studies estimate the Ashkenazi Jewish founder generation at around 150 families. Research has suggested that only a third of the original mitochondrial DNA (mtDNA) signatures survived. Unlike isolated populations, founder groups surrounded by larger populations tend to absorb mtDNA from the host population. A prior study reported that a significant portion of Ashkenazi Jews carry mtDNA of ancient European origin, leading to the hypothesis that the female founders were primarily European, while male founders were Near Eastern.

This study presents a method to distinguish between founder and absorbed mtDNA lineages in contemporary Ashkenazi Jews. Adjusting the sample size, absorbed lineages appear as singletons, while founder lineages show multiple occurrences. Our analysis found that less than 15 % of current Ashkenazi Jews carry absorbed mtDNA, consistent with patterns seen in many founder populations, where absorbed matrilineal lineages outnumber founder ones. However, this does not support a non-Jewish European origin for the founding generation.

Given that Y-chromosome analysis already confirms a Near Eastern origin for Ashkenazi paternal lineages, we propose that both maternal and paternal lineages share a common Near Eastern ancestry. This challenges the convoluted hypothesis of a mixed origin with Near Eastern paternal and predominantly European maternal founders. Our results reinforce the genetic evidence of a unified founding population and strongly favor a straightforward model consisting of a Near Eastern origin for both maternal and paternal founding lineages,

创始人群体的创始一代的规模通常很小。例如，研究估计德系犹太人的创始一代大约有150个家庭。研究表明，只有三分之一的原始线粒体DNA （mtDNA）特征存活了下来。与孤立的种群不同，被较大种群包围的创始者群体倾向于从宿主种群吸收mtDNA。先前的一项研究报告称，很大一部分德系犹太人携带古代欧洲血统的mtDNA，这导致了女性创始人主要是欧洲人，而男性创始人则是近东人的假设。本研究提出了一种方法来区分创始人和吸收的mtDNA谱系在当代德系犹太人。调整样本量后，吸收谱系表现为单例，而创立谱系表现为多例。我们的分析发现，目前只有不到15%的德系犹太人携带被吸收的mtDNA，这与在许多创始人群体中看到的模式一致，在这些人群中，被吸收的母系血统多于创始人血统。然而，这并不支持非犹太人的欧洲血统。鉴于y染色体分析已经证实了德系犹太人父系的近东起源，我们提出母系和父系都有共同的近东祖先。这挑战了一个复杂的假设，即一个由近东父亲和主要是欧洲母亲组成的混合起源。我们的研究结果加强了统一的创始人群的遗传证据，并强烈支持一个直接的模型，包括母亲和父亲的创始谱系的近东起源。

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引用次数: 0

Influence of metformin on the expression of SESTRIN2, Nrf2, and TUG1 genes in the liver tissue of diabetic rats 二甲双胍对糖尿病大鼠肝组织中SESTRIN2、Nrf2、TUG1基因表达的影响

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-26 DOI: 10.1016/j.humgen.2025.201434

Roya Zanganeh , Hamed Fanaei , Anis saadatmand , Ali dashtkar , Mohsen Saravani

Background

This study, focusing on the role of metformin in reducing oxidative stress, examined the effects of this drug on the expression of stress-related genes SESTRIN2, Nrf2, and TUG1 in the liver of diabetic rats.

Methods

Animals (n = 30) were divided into four groups: a control group (C), a control group treated with metformin (400 mg/kg/day) (C + M), a diabetic group (D), and a diabetic group treated with metformin (D + M) (400 mg/kg/day). Streptozotocin (STZ) was injected to induce diabetes. Serum levels of fasting blood glucose (FBG), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDLC), total cholesterol (TC), and insulin were measured. Gene expression was assessed using the RT-PCR technique.

Results

The expression levels of Nrf2 and SESTRIN2 were decreased in group D compared to groups C and C + M but were not statistically significant (p > 0.05). However, the expression of Nrf2 and SESTRIN2 was increased in group D + M compared to group D, but only for Nrf2 was it significant (p = 0.0164). In addition, the expression of Nrf2 was significantly increased in group D + M compared to group C (p = 0.0299). The expression of TUG1 was increased in group D compared to group C, while the D + M group (1.36 ± 0.43) showed a decrease in TUG1 expression compared to group D (3 ± 1.64), which was not statistically significant. In addition, MET reduced the insulin resistance index, FBG, and lipid profile in the D + M group compared to the D group.

Discussion

Metformin suppresses oxidative stress by activating antioxidant pathways through increasing NRF2 gene expression, thereby improving diabetes and playing a protective role in the liver.

本研究以二甲双胍为研究对象，研究了二甲双胍对糖尿病大鼠肝脏应激相关基因SESTRIN2、Nrf2和TUG1表达的影响。方法30只动物分为4组：对照组(C)、二甲双胍（400 mg/kg/ D）治疗组（C + M）、糖尿病组(D)和糖尿病组（D + M）治疗组（400 mg/kg/ D）。注射链脲佐菌素（STZ）诱导糖尿病。测定空腹血糖（FBG）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDLC）、总胆固醇（TC）、胰岛素水平。采用RT-PCR技术检测基因表达。结果D组Nrf2、SESTRIN2表达水平较C、C + M组降低，但差异无统计学意义(p >；0.05)。D + M组Nrf2和SESTRIN2的表达较D组增加，但只有Nrf2表达显著（p = 0.0164）。与C组相比，D + M组Nrf2的表达显著升高（p = 0.0299）。D组TUG1表达较C组升高，D + M组TUG1表达（1.36±0.43）较D组（3±1.64）降低，差异无统计学意义。此外，与D组相比，MET降低了D + M组的胰岛素抵抗指数、FBG和血脂。讨论二甲双胍通过增加NRF2基因表达激活抗氧化途径抑制氧化应激，从而改善糖尿病，对肝脏起到保护作用。

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引用次数: 0

miR-151 in health and disease: A comprehensive review of its implications in Cancer, diabetes, and more miR-151在健康和疾病中的作用：对其在癌症、糖尿病等疾病中的意义的全面综述

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-26 DOI: 10.1016/j.humgen.2025.201443

Pourya Ahmadi , Fatemeh Eizadifard , Parsa Pahlavan , Majid Tafrihi

Background

MicroRNAs (miRNAs) are key post-transcriptional regulators involved in numerous physiological and pathological processes.

Purpose

This review focuses on miR-151, a functionally versatile miRNA, and synthesizes current evidence regarding its involvement across a spectrum of human diseases.

Main findings

miR-151 has been shown to play a dual role as both an oncogene and a tumor suppressor, depending on the cellular context and disease type. Its dysregulation has been implicated in the development and progression of various conditions, including multiple cancers, diabetes, osteoarthritis, cardiovascular disorders, intracranial aneurysms, and male infertility. Through modulation of target genes and signaling pathways, miR-151 influences cell proliferation, migration, apoptosis, and epithelial–mesenchymal transition. Importantly, its tissue-specific expression and regulatory dynamics underscore its potential as a diagnostic biomarker and therapeutic target.

Conclusion

By compiling and analyzing current research, this review aims to clarify the multifaceted roles of miR-151 in disease pathogenesis and to encourage further studies that may support its translational application in precision medicine.

micrornas （miRNAs）是参与许多生理和病理过程的关键转录后调控因子。目的：本文综述了miR-151这一功能多样的miRNA，并综合了目前关于其参与一系列人类疾病的证据。主要发现smir -151已被证明在细胞环境和疾病类型上发挥致癌基因和肿瘤抑制基因的双重作用。它的失调与多种疾病的发生和发展有关，包括多种癌症、糖尿病、骨关节炎、心血管疾病、颅内动脉瘤和男性不育症。通过调控靶基因和信号通路，miR-151影响细胞增殖、迁移、凋亡和上皮-间质转化。重要的是，其组织特异性表达和调控动态强调了其作为诊断生物标志物和治疗靶点的潜力。通过对现有研究的整理和分析，本文旨在阐明miR-151在疾病发病机制中的多方面作用，并鼓励进一步的研究，以支持其在精准医学中的转化应用。

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引用次数: 0

Potential of micro-RNAs 193a-3p, 378-3p, 210-3p, and 362-3p as serum biomarkers for clear cell renal cell carcinoma 微rna 193a-3p、378-3p、210-3p和362-3p作为透明细胞肾细胞癌血清生物标志物的潜力

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-25 DOI: 10.1016/j.humgen.2025.201444

Benedikt Ewig , Thomas Büttner , Glen Kristiansen , Doris Schmidt , Jörg Ellinger , Stefan Hauser

Objective

MicroRNAs (miRs) play a significant role in carcinogenesis and tumor progression, suggesting their potential as biomarkers. This study aimed to evaluate the diagnostic utility of four circulating miRs in patients with clear cell renal cell carcinoma (ccRCC).

Methods

Serum expression levels of miR-193a-3p, miR-378-3p, miR-210-3p, and miR-362-3p were quantified in 30 patients with clear cell renal cell carcinoma (ccRCC) and 15 non-tumor controls using real-time polymerase chain reaction. Mann–Whitney U tests and Receiver Operating Characteristics with Area under the curve (AUC) calculations were employed to evaluate the association between miR expression levels and patient group (ccRCC versus controls).

Results

Statistically significant differences in mean serum levels of miR-193a-3p and miR-378-3p were observed between ccRCC patients and controls. The median miR-193a-3p level was increased in ccRCC patients (median: 4.50 %, IQR: 1.38, 11.47) compared to controls (median: 2.57 %, IQR: 0.27, 3.87), p = 0.032; AUC for ccRCC detection was 0.70. Also, the median miR-378-3p level was higher in ccRCC patients (median: 2.01 %, IQR: 1.00, 3.33) compared to controls (median: 0.66 %, IQR: 0.44, 1.98), p = 0.049. AUC was 0.68. No significant differences were found for serum miR-362-3p and miR-210-3p expression in ccRCC patients and non-tumor controls (p = 0.547 for miR-362-3p and p = 0.791 for miR-210-3p).

Conclusion

These findings suggest that miR-193a-3p and miR-378-3p may have limited potential as diagnostic biomarkers for ccRCC. The data do not support further investigation of miR-362-3p and miR-210-3p for this purpose.

目的：micrornas （miRs）在癌变和肿瘤进展中发挥重要作用，提示其作为生物标志物的潜力。本研究旨在评估四种循环miRs在透明细胞肾细胞癌（ccRCC）患者中的诊断价值。方法采用实时聚合酶链反应法测定30例透明细胞肾细胞癌（ccRCC）患者和15例非肿瘤对照组血清中miR-193a-3p、miR-378-3p、miR-210-3p和miR-362-3p的表达水平。采用Mann-Whitney U检验和曲线下面积（AUC）计算的受试者操作特征来评估miR表达水平与患者组（ccRCC与对照组）之间的关系。结果ccRCC患者血清miR-193a-3p、miR-378-3p水平与对照组比较差异均有统计学意义。与对照组（中位数：2.57%,IQR: 0.27, 3.87）相比，ccRCC患者中位miR-193a-3p水平升高（中位数：4.50%,IQR: 1.38, 11.47）， p = 0.032；ccRCC检测的AUC为0.70。此外，ccRCC患者中位miR-378-3p水平（中位数：2.01%,IQR: 1.00, 3.33）高于对照组（中位数：0.66%,IQR: 0.44, 1.98）， p = 0.049。AUC为0.68。血清miR-362-3p和miR-210-3p在ccRCC患者和非肿瘤对照组中表达无显著差异（miR-362-3p p = 0.547, miR-210-3p p = 0.791）。这些发现表明miR-193a-3p和miR-378-3p作为ccRCC的诊断生物标志物可能潜力有限。数据不支持为此目的进一步研究miR-362-3p和miR-210-3p。

{"title":"Potential of micro-RNAs 193a-3p, 378-3p, 210-3p, and 362-3p as serum biomarkers for clear cell renal cell carcinoma","authors":"Benedikt Ewig , Thomas Büttner , Glen Kristiansen , Doris Schmidt , Jörg Ellinger , Stefan Hauser","doi":"10.1016/j.humgen.2025.201444","DOIUrl":"10.1016/j.humgen.2025.201444","url":null,"abstract":"<div><h3>Objective</h3><div>MicroRNAs (miRs) play a significant role in carcinogenesis and tumor progression, suggesting their potential as biomarkers. This study aimed to evaluate the diagnostic utility of four circulating miRs in patients with clear cell renal cell carcinoma (ccRCC).</div></div><div><h3>Methods</h3><div>Serum expression levels of miR-193a-3p, miR-378-3p, miR-210-3p, and miR-362-3p were quantified in 30 patients with clear cell renal cell carcinoma (ccRCC) and 15 non-tumor controls using real-time polymerase chain reaction. Mann–Whitney <em>U</em> tests and Receiver Operating Characteristics with Area under the curve (AUC) calculations were employed to evaluate the association between miR expression levels and patient group (ccRCC versus controls).</div></div><div><h3>Results</h3><div>Statistically significant differences in mean serum levels of miR-193a-3p and miR-378-3p were observed between ccRCC patients and controls. The median miR-193a-3p level was increased in ccRCC patients (median: 4.50 %, IQR: 1.38, 11.47) compared to controls (median: 2.57 %, IQR: 0.27, 3.87), <em>p</em> = 0.032; AUC for ccRCC detection was 0.70. Also, the median miR-378-3p level was higher in ccRCC patients (median: 2.01 %, IQR: 1.00, 3.33) compared to controls (median: 0.66 %, IQR: 0.44, 1.98), <em>p</em> = 0.049. AUC was 0.68. No significant differences were found for serum miR-362-3p and miR-210-3p expression in ccRCC patients and non-tumor controls (<em>p</em> = 0.547 for miR-362-3p and <em>p</em> = 0.791 for miR-210-3p).</div></div><div><h3>Conclusion</h3><div>These findings suggest that miR-193a-3p and miR-378-3p may have limited potential as diagnostic biomarkers for ccRCC. The data do not support further investigation of miR-362-3p and miR-210-3p for this purpose.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201444"},"PeriodicalIF":0.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing DNA damage in fresh versus frozen blood from healthy individuals and patients with obesity in Egypt 比较埃及健康人与肥胖患者新鲜血液与冷冻血液中的DNA损伤

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-23 DOI: 10.1016/j.humgen.2025.201441

Peter S.F. Erian , Rania M.A. Abdel Kader , Safinaz E. Eltoukhy

The use of alkaline comet assay has increased in DNA damage assessment in various non-communicable diseases and epidemiological studies, which, in turn, requires a large sample size. Our objective is to compare the damage of DNA using comet assay in healthy individuals versus patients with obesity and to evaluate the feasibility of using frozen whole blood samples as a simple solution for the need for large sample size. Based on this study and previous literature, using frozen whole blood samples in the comet assay technique is a simple and feasible approach that can be readily applied in biomonitoring and epidemiological studies. Furthermore, this study compared comet tail length in healthy individuals and patients with obesity, revealing greater DNA damage in patients with obesity samples, which denotes a higher risk of mutations, chromosomal abnormalities, and cancer. Further enhancements and validation are recommended for technique improvement, and further studies of DNA damage in various non-communicable diseases, including obesity, are also recommended.

在各种非传染性疾病和流行病学研究中，使用碱性彗星测定法增加了DNA损伤评估，这反过来又需要大量样本。我们的目的是比较健康个体和肥胖患者使用彗星测定法的DNA损伤，并评估使用冷冻全血样本作为需要大样本量的简单解决方案的可行性。基于本研究和以往文献，冷冻全血在彗星分析技术中是一种简单可行的方法，可以很容易地应用于生物监测和流行病学研究。此外，该研究比较了健康个体和肥胖患者的彗星尾巴长度，揭示了肥胖患者样本中更大的DNA损伤，这表明突变、染色体异常和癌症的风险更高。建议进一步加强和验证技术改进，并建议进一步研究包括肥胖在内的各种非传染性疾病的DNA损伤。

引用次数: 0

βS haplotypes: Genetic profile and association with biochemical parameters in individuals with Sickle cell anemia in Western Bahia, Brazil βS单倍型：巴西西巴伊亚镰状细胞性贫血患者的遗传特征及其与生化参数的关系

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-18 DOI: 10.1016/j.humgen.2025.201438

Ilana Luize Rocha Santana , Raphael Magalhães , Victoria Simões Bernardo , Manoel Ferreira de Magalhães Filho , Pâmela Lourdes Pereira da Silva , Larissa Paola Rodrigues Venancio

Sickle cell anemia (SCA) is a hemoglobinopathy with a heterogeneous clinical presentation that, in part, results from complex interactions between genetic factors, some of which are explained by haplotypes in the β-globin (β^S) gene cluster. This study identified the main haplotypic profiles of individuals with SCA in Western Bahia, Brazil, and evaluates the possible relationship between the genetic profile associated with haplotype inheritance and clinical follow-up parameters presented by the individuals participating in the study. The Bantu/Benin genotype was more frequent, although it did not show a statistically significant difference compared to the Bantu/Bantu genotype. As described in other locations in Brazil, the Bantu chromosome was the most frequent in this study (59 %), which supports the data on the formation and dynamics of the population concerning the geographical origin of the enslaved Africans trafficked to the capital of Western Bahia. Important hematological parameters, such as HbF, biochemical parameters associated with the hemolysis process, and phenotype severity, such as lactate dehydrogenase, aspartate aminostransferase, and direct bilirubin, were related to the Bantu/Bantu genotype. HbF levels were 4× lower, and biochemical parameters were up to 2.5× higher in Bantu/Bantu individuals who did not use hydroxycarbamide (HC) compared to carriers of the Bantu/Bantu genotype who used HC. The results indicate the importance of assessing the inheritance of β^S-haplotypes to help understand the phenotype and the relevance of HC use in the context of SCA.

镰状细胞性贫血（SCA）是一种具有异质临床表现的血红蛋白病，其部分原因是遗传因素之间复杂的相互作用，其中一些可以用β-珠蛋白（βS）基因簇中的单倍型来解释。本研究确定了巴西西巴伊亚州SCA个体的主要单倍型谱，并评估了参与研究的个体所呈现的与单倍型遗传相关的遗传谱与临床随访参数之间的可能关系。班图/贝宁基因型更常见，尽管与班图/班图基因型相比没有统计学上的显著差异。正如在巴西其他地区所描述的那样，班图染色体在本研究中是最常见的（59%），这支持了有关人口形成和动态的数据，这些数据与贩卖到西巴伊亚首都的被奴役非洲人的地理起源有关。重要的血液学参数，如HbF，与溶血过程相关的生化参数，以及表型严重程度，如乳酸脱氢酶、天冬氨酸氨基转移酶和直接胆红素，都与班图/班图基因型有关。与使用羟脲（HC）的班图/班图基因型携带者相比，不使用羟脲（HC）的班图/班图人HbF水平低4倍，生化参数高2.5倍。结果表明，评估β s单倍型的遗传对于帮助理解SCA背景下HC使用的表型和相关性具有重要意义。

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引用次数: 0

Genetic expression of NKX2-5 gene among first trimester pregnancy loss NKX2-5基因在妊娠早期流产中的表达

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-18 DOI: 10.1016/j.humgen.2025.201439

Muraleedharan Santhamma Dhanya , Selvaraj Karthick , Reba Babu Alex , Anandhi Dhanavel , Shaiju Basheer , Sreeja Sreenivasan , Rajitha Puthiya Purayil , Divakaran Dinesh Roy

First-trimester pregnancy loss is a serious public health problem, affecting both physical and mental well-being. Occurring in 10–15 % of clinically recognized pregnancies, it remains a critical issue in reproductive health. Genetic factors impacting fetal development and maternal inflammatory responses are linked to early pregnancy loss. This case-control study included 120 participants: 60 cases (including maternal samples for evaluating inflammatory markers and their products of conception or terminated fetuses without normal cardiac activity or suspected congenital heart defects for the evaluation of NKX2–5 gene expression) and 60 healthy mothers having one or two live children without any congenital heart defects as controls. Inflammatory markers CRP and IL-6 were measured using ELISA kits. Gene expression of NKX2–5 was quantified by real-time PCR after RNA extraction from products of conception or terminated fetuses, cDNA synthesis, and amplification using specific primers. Relative expression was calculated using the 2^(-ΔΔCt) method. The findings revealed significantly higher CRP and IL-6 levels in cases than controls (p < 0.001) and changes in NKX2–5 expression. The results indicate a significant increase in NKX2–5 expression in products of conception from women with early pregnancy loss compared to those with healthy pregnancies (p < 0.05). Increased maternal levels of TSH were also revealed to be an independent predictor for early abortion (OR = 3.57, p = 0.004). Our findings suggest that NKX2–5 gene deregulation and inflammation in the maternal compartment can play a role in early pregnancy loss as future candidate targets for both diagnostic and treatment intervention.

妊娠早期流产是一个严重的公共卫生问题，影响着身体和精神健康。在临床确认的怀孕中，有10 - 15%发生这种情况，它仍然是生殖健康中的一个严重问题。影响胎儿发育和母体炎症反应的遗传因素与早孕流产有关。本病例对照研究包括120名参与者：60例（包括用于评估炎症标志物及其产物的母体样本，用于评估无正常心脏活动或疑似先天性心脏缺陷的妊娠或终止胎儿，用于评估NKX2-5基因表达）和60例健康母亲，她们有一个或两个没有任何先天性心脏缺陷的活产儿作为对照。采用ELISA试剂盒检测炎症标志物CRP和IL-6。从受胎或终止胎的产物中提取RNA，合成cDNA，并使用特定引物扩增后，采用实时荧光定量PCR技术测定NKX2-5的基因表达。相对表达式采用2^（-ΔΔCt）方法计算。结果显示，病例中CRP和IL-6水平明显高于对照组(p <；0.001)和NKX2-5表达的变化。结果表明，与健康妊娠妇女相比，早期妊娠流产妇女的受精卵中NKX2-5的表达显著增加(p <；0.05)。母体TSH水平升高也是早期流产的独立预测因子（OR = 3.57, p = 0.004）。我们的研究结果表明，NKX2-5基因失调和母体间室炎症可能在早期妊娠丢失中发挥作用，作为未来诊断和治疗干预的候选目标。

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引用次数: 0

Autophagy protein 5 (ATG5) rs573775 protects Malaysian Malay women from systemic lupus erythematosus 自噬蛋白5 (ATG5) rs573775保护马来西亚马来妇女免受系统性红斑狼疮

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-16 DOI: 10.1016/j.humgen.2025.201435

Hwa Chia Chai, Kek Heng Chua

Objective

Autophagy is one of the critical cellular processes implicated in the pathogenesis of SLE. Polymorphisms in the autophagy-related genes have been associated with increased susceptibility to SLE, particularly variations in the autophagy protein 5 (ATG5) gene which has been associated with SLE in several populations. This case-control study aimed to investigate the association between polymorphisms in ATG5 and SLE in Malaysian population.

Methods

Tetra primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to genotype ATG5 rs6937876, rs4945747, rs573775, rs2245214 and rs548234 in 233 SLE patients and 224 healthy controls, collected from 2000 to 2015.

Results

In the overall Malaysian population, AG genotype (adjusted p = 0.013, OR = 1.327, 95 % CI: 1.040 to 1.695) of rs6937876 were significantly associated with increased SLE susceptibility. The dominant model (AG + AA) (adjusted p = 0.006, OR = 0.671, 95 % CI: 0.464 to 0.972), additive model (adjusted p = 0.005, OR = 0.462, 95 % CI: 0.291 to 0.733), and minor A allele (adjusted p = 0.007, OR = 0.628, 95 % CI: 0.447 to 0.882) of rs573775 significantly associated with Malay population by providing protection against SLE.

Conclusion

The SNPs in ATG5 seem to not only conferring SLE susceptibility to the Malaysian population but also protect them from SLE. Gene expression of these SNPs and their interactions with upstream or downstream genes and microenvironment in the Malaysian population, especially Malays, is worth further study.

目的自噬是参与SLE发病的关键细胞过程之一。自噬相关基因的多态性与SLE易感性增加有关，特别是自噬蛋白5 （ATG5）基因的变异，在一些人群中与SLE相关。本病例对照研究旨在调查马来西亚人群中ATG5多态性与SLE之间的关系。方法对2000 ~ 2015年收集的233例SLE患者和224例健康对照进行ATG5 rs6937876、rs4945747、rss573775、rs2245214和rss548234基因型分析。结果在马来西亚总体人群中，rs6937876的AG基因型（调整p = 0.013, OR = 1.327, 95% CI: 1.040 ~ 1.695）与SLE易感性增加显著相关。优势模型（AG + AA）（调整p = 0.006, OR = 0.671, 95% CI: 0.464 ~ 0.972）、加性模型（调整p = 0.005, OR = 0.462, 95% CI: 0.291 ~ 0.733）和次要A等位基因（调整p = 0.007, OR = 0.628, 95% CI: 0.447 ~ 0.882）的rs573775通过提供SLE保护与马来人群显著相关。结论ATG5的snp似乎不仅赋予马来西亚人群SLE易感性，而且保护他们免受SLE。这些snp的基因表达及其与上游或下游基因和微环境的相互作用值得进一步研究，特别是马来人。

{"title":"Autophagy protein 5 (ATG5) rs573775 protects Malaysian Malay women from systemic lupus erythematosus","authors":"Hwa Chia Chai, Kek Heng Chua","doi":"10.1016/j.humgen.2025.201435","DOIUrl":"10.1016/j.humgen.2025.201435","url":null,"abstract":"<div><h3>Objective</h3><div>Autophagy is one of the critical cellular processes implicated in the pathogenesis of SLE. Polymorphisms in the autophagy-related genes have been associated with increased susceptibility to SLE, particularly variations in the autophagy protein 5 (<em>ATG5</em>) gene which has been associated with SLE in several populations. This case-control study aimed to investigate the association between polymorphisms in <em>ATG5</em> and SLE in Malaysian population.</div></div><div><h3>Methods</h3><div>Tetra primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to genotype <em>ATG5</em> rs6937876, rs4945747, rs573775, rs2245214 and rs548234 in 233 SLE patients and 224 healthy controls, collected from 2000 to 2015.</div></div><div><h3>Results</h3><div>In the overall Malaysian population, AG genotype (adjusted <em>p</em> = 0.013, OR = 1.327, 95 % CI: 1.040 to 1.695) of rs6937876 were significantly associated with increased SLE susceptibility. The dominant model (AG + AA) (adjusted <em>p</em> = 0.006, OR = 0.671, 95 % CI: 0.464 to 0.972), additive model (adjusted <em>p</em> = 0.005, OR = 0.462, 95 % CI: 0.291 to 0.733), and minor A allele (adjusted <em>p</em> = 0.007, OR = 0.628, 95 % CI: 0.447 to 0.882) of rs573775 significantly associated with Malay population by providing protection against SLE.</div></div><div><h3>Conclusion</h3><div>The SNPs in <em>ATG5</em> seem to not only conferring SLE susceptibility to the Malaysian population but also protect them from SLE. Gene expression of these SNPs and their interactions with upstream or downstream genes and microenvironment in the Malaysian population, especially Malays, is worth further study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201435"},"PeriodicalIF":0.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A study conducted in breast cancer cells found that (valproic acid) inhibits CIP2A/c-MYC/PI3K/Akt/mTOR signaling molecules and PD-L1 一项对乳腺癌细胞的研究发现，丙戊酸可抑制CIP2A/c-MYC/PI3K/Akt/mTOR信号分子和PD-L1

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-06-15 DOI: 10.1016/j.humgen.2025.201437

Elahe Zeinali , Vahid Bagheri , Esmaeil Rostami , Gholamreza Anani Sarab

Resistant cells significantly undermine the efficacy of breast cancer treatment. CIP2A and PD-L1 are among the major therapeutic challenges in breast cancer, as they are key drivers of drug resistance and immune evasion, respectively. Hence, identifying agents—particularly epigenetic drugs—that can suppress these factors by altering gene expression is of great interest. This study aimed to evaluate the molecular mechanisms and effects of valproic acid (VPA), a histone deacetylase inhibitor, on CIP2A and PD-L1 expression in the MCF-7 breast cancer cell line. VPA inhibited MCF-7 cell proliferation in a dose- and time-dependent manner. Treatment with VPA resulted in downregulation of CIP2A and its downstream signaling molecules c-MYC, PI3K, AKT, and mTOR. Moreover, VPA treatment reduced PD-L1 expression in MCF-7 cells. These findings suggest that VPA may offer a novel approach to addressing challenges associated with CIP2A and PD-L1. Therefore, either as a monotherapy or in combination with existing treatments, VPA could represent a promising strategy for enhancing the efficacy of breast cancer therapy.

耐药细胞显著地破坏了乳腺癌治疗的效果。CIP2A和PD-L1是乳腺癌的主要治疗挑战之一，因为它们分别是耐药和免疫逃避的关键驱动因素。因此，寻找能够通过改变基因表达来抑制这些因素的药物，尤其是表观遗传药物，是人们非常感兴趣的。本研究旨在探讨组蛋白去乙酰化酶抑制剂丙戊酸（VPA）对MCF-7乳腺癌细胞系CIP2A和PD-L1表达的影响及其分子机制。VPA抑制MCF-7细胞增殖呈剂量和时间依赖性。VPA处理导致CIP2A及其下游信号分子c-MYC、PI3K、AKT和mTOR下调。此外，VPA处理降低了MCF-7细胞中PD-L1的表达。这些发现表明，VPA可能为解决CIP2A和PD-L1相关的挑战提供了一种新的方法。因此，无论是作为单一疗法还是与现有疗法联合使用，VPA都可能是一种很有前景的提高乳腺癌治疗效果的策略。

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