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Altered expression of long non-coding RNAs NRON and SNHG11 in patients with ischemic stroke 缺血性中风患者体内长非编码 RNA NRON 和 SNHG11 的表达改变
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-25 DOI: 10.1186/s43042-024-00482-w
Negin Gharbi, Hamideh Mahmoudinasab, Etrat Hooshmandi, Mousa Rahimi, Mahnaz Bayat, Najmeh Karimi, Seyedeh Shamim Hojati, Zoofa Zayani, Reza Tabrizi, Afshin Borhani-Haghighi
Long non-coding RNAs, known as LncRNAs, have demonstrated a robust association with the pathogenesis of stroke. NRON and SNHG are among the most extensively studied lncRNAs in the context of atherosclerosis and inflammatory conditions. Given the absence of a current pathophysiological hypothesis regarding the potential relevance of the SNHG family and NRON lncRNAs in ischemic stroke (IS), this study aimed to investigate the altered expression of NRON and SNHG11 following atherosclerotic ischemic stroke (AIS) and their potential association with the risk of AIS. Blood samples were collected from 65 AIS patients (with large artery atherosclerosis or small vessel disease) and 65 controls. The expression levels of NRON and SNHG11 were assessed within the first 24 h following the stroke using quantitative real-time PCR. NRON expression exhibited a significant decrease in patients compared to controls, while no substantial difference was observed in the expression level of SNHG11 between the two groups. Furthermore, logistic regression analysis revealed a significant negative association between NRON expression and the risk of AIS (adjusted odds ratio = 0.70; 95% confidence interval 0.55–0.89, P = 0.004). These findings suggest that NRON may play a role in the pathogenesis of AIS and could potentially serve as a biomarker for the disease. To fully comprehend the mechanism underlying the association between NRON and AIS and to explore its potential therapeutic implications, further investigation is warranted.
被称为 LncRNA 的长非编码 RNA 与中风的发病机制有着密切的联系。NRON和SNHG是在动脉粥样硬化和炎症条件下研究最广泛的lncRNA之一。鉴于目前还没有关于 SNHG 家族和 NRON lncRNA 与缺血性中风(IS)潜在相关性的病理生理学假说,本研究旨在调查动脉粥样硬化性缺血性中风(AIS)后 NRON 和 SNHG11 表达的改变及其与 AIS 风险的潜在关联。本研究采集了65名AIS患者(大动脉粥样硬化或小血管疾病)和65名对照者的血样。采用定量实时 PCR 技术评估了中风后 24 小时内 NRON 和 SNHG11 的表达水平。与对照组相比,患者的 NRON 表达明显下降,而 SNHG11 的表达水平在两组之间没有发现明显差异。此外,逻辑回归分析显示,NRON表达与AIS风险之间存在显著的负相关(调整后的几率比=0.70;95%置信区间为0.55-0.89,P=0.004)。这些发现表明,NRON可能在AIS的发病机制中发挥作用,并有可能成为该疾病的生物标志物。为了充分理解NRON与AIS之间的关联机制,并探索其潜在的治疗意义,还需要进一步的研究。
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引用次数: 0
Association of common variant rs9934336 of SLC5A2 (SGLT2) gene with SARS-CoV-2 infection and mortality SLC5A2(SGLT2)基因的常见变异体 rs9934336 与 SARS-CoV-2 感染和死亡率的关系
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-24 DOI: 10.1186/s43042-024-00481-x
Anamika Das, Gunanidhi Dhangadamajhi
COVID-19 has its life-threatening complications more pronounced in people with underlying health conditions such as diabetes, cardiovascular disease and kidney disease. Inhibition of the sodiumglucose cotransporter 2 (SGLT2), which primarily increases urinary glucose excretion, is shown to be beneficial in patients with type 2 diabetes mellitus (T2D) and other comorbidities. SGLT2 is encoded by SLC5A2 gene, and of the several genetic variants, SNP rs9934336 is gaining importance for being associated with reduced HbA1c level and lower incidence of T2D. Since a complex bidirectional relationship exists between COVID-19 and hyperglycaemia, we conducted a worldwide association study to investigate the effect of rs9934336 on COVID-19 outcomes. Worldwide prevalence data of SLC5A2 SNP rs9934336 were obtained from relevant published articles and databases for genomic variants. COVID-19 data procured from the Worldometer website were used for conducting Spearman’s correlation analysis with minor allele frequency data of rs9934336. Significant positive correlation was observed between rs9934336 and COVID-19 incidence (p < 0.0001, r = 0.6225) as well as deaths (p < 0.0001, r = 0.5837). The present finding of significant association of SLC5A2 variant rs9934336 with COVID-19 risk has to be validated by case–control studies in diverse populations along with other variants regulating the expression and function of SGLT2.
COVID-19 在患有糖尿病、心血管疾病和肾脏疾病等基础疾病的人群中,其危及生命的并发症更为明显。钠-葡萄糖共转运体 2(SGLT2)主要增加尿糖排泄,抑制它对 2 型糖尿病(T2D)和其他合并症患者有益。SGLT2 由 SLC5A2 基因编码,在几种基因变异中,SNP rs9934336 因与 HbA1c 水平降低和 T2D 发病率降低相关而日益受到重视。由于 COVID-19 与高血糖之间存在复杂的双向关系,我们开展了一项全球关联研究,以调查 rs9934336 对 COVID-19 结果的影响。SLC5A2 SNP rs9934336 的全球流行率数据来自相关发表文章和基因组变异数据库。利用从 Worldometer 网站获取的 COVID-19 数据与 rs9934336 的小等位基因频率数据进行斯皮尔曼相关性分析。结果表明,rs9934336 与 COVID-19 发病率(p < 0.0001,r = 0.6225)和死亡率(p < 0.0001,r = 0.5837)之间存在显著的正相关。本研究发现 SLC5A2 变体 rs9934336 与 COVID-19 风险有明显关联,这一发现还需要在不同人群中进行病例对照研究,并与其他调节 SGLT2 表达和功能的变体一起进行验证。
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引用次数: 0
CD36 gene variant rs1761667(G/A) as a biomarker in obese type 2 diabetes mellitus cases 作为肥胖 2 型糖尿病病例生物标志物的 CD36 基因变异 rs1761667(G/A)
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-24 DOI: 10.1186/s43042-024-00478-6
Ashwin Kumar Shukla, Amreen Shamsad, Atar Singh Kushwah, Shalini Singh, Kauser Usman, Monisha Banerjee
Several reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects. Blood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software. Fasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association (P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated (P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases. The risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker.
一些报告讨论了与肥胖相关的 CD36 基因型与 2 型糖尿病(T2DM)发病之间的联系。因此,本研究探讨了 CD36 多态性 rs1761667 (G/A) 在肥胖 T2DM 患者中的预后价值。研究还探讨了该基因变异与受试者临床/生化指标之间的相关性。根据纳入/排除标准,研究人员从勒克瑙 KGMU 医学系门诊部(OPD)采集了印度北部共 475 名受试者的血样。对 250 例 T2DM 病例、75 例肥胖 T2DM 病例和 150 例对照者的人体测量细节进行了记录,并对生化指标进行了估计。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,利用特定引物和 HhaI 酶对 CD36 基因变异体 rs1761667 (G/A) 进行了基因型分析。所有统计分析均使用 SPSS(21.0 版)和 Prism(5.01)软件进行。T2DM 受试者的空腹血糖(FPG)、收缩压(SBP)和餐后血糖(PPG)均有显著性差异。总胆固醇(TC)、低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL)等血脂谱也被发现与肥胖 T2DM 病例显著相关。rs1761667(G/A)的 GA 和 AA 基因型在肥胖 T2DM 病例中显示出显著的相关性。GA 基因型与 T2DM 高风险易感性增加 2.77 倍有相当大的关联(P < 0.001)。研究发现,AA 基因型与肥胖 T2DM 风险增加 2.94 倍显著相关(P = 0.008),而 T2DM 病例发生肥胖的风险增加 9.33 倍。通过对 CD36 基因变异体 rs1761667(G/A)进行基因分型,可以评估 T2DM 病例的肥胖风险。然而,FPG、PPG、TC、LDL 和 VLDL 的升高表明肥胖 T2DM 病例的预后较差。CD36基因变异可作为预测T2DM和肥胖症风险的预后生物标志物,而人类生化风险因素可作为预防生物标志物。
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引用次数: 0
In silico analysis of mutation spectrum of Ehlers–Danlos, osteogenesis imperfecta, and cutis laxa overlapping phenotypes in Iranian population 伊朗人群中埃尔斯-丹洛斯症、成骨不全症和皮肤松弛症重叠表型突变谱的硅学分析
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-23 DOI: 10.1186/s43042-024-00479-5
Teymoor Khosravi, Karim Naghipoor, Fatemeh Vaghefi, Ali Mohammad Falahati, Morteza Oladnabi
Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Some of their subtypes are inherited in autosomal recessive patterns, so they are expected to be prevalent in populations like Iran, where consanguineous marriages are common. In the current work, a cohort of Iranian patients with overlapping phenotypes of the EDS/OI/CL and their mutation spectrum was defined. Based on this, in silico analysis was conducted to anticipate further probable genetic variations. Pathogenicity of EDS, OI, and CL variants in Iranian patients was evaluated using Web servers. A protein interaction network was created by String database and visualized using a Python-based library. The Iranome database was used to predict other genetic mutations in all reported genes of EDS, OI, and CL syndromes. In the EDS/OI/CL overlap phenotype, 32 variants in 18 genes have been involved. At least 59% of patients were from families with consanguineous marriages. Interaction analysis showed that COL1A1, COL1A2, CRTAP, LEPRE1, PLOD1, and ADAMTS2 have the most significant impact within the protein network of EDS/OI/CL overlap phenotype. Analyzing the Iranome database revealed 46 variants of EDS, OI, and CL genes potentially disease causing. The overlapping phenotype of EDS, OI, and CL syndromes requires genetic testing (e.g., whole-exome sequencing) to reveal respective variants, which helps to diagnose more accurately and manage the disease more effectively. Particularly in populations with high rates of consanguineous marriages, such as Iran, genetic screening plays a crucial role in premarital and prenatal counseling to prevent the transmission of these rare connective tissue disorders.
埃勒斯-丹洛斯综合征(EDS)、成骨不全症(OI)和皮肤松弛症(CL)是三种罕见的异质性结缔组织疾病。这些综合征的患者具有相似的表现和难以预测的预后,因此极有可能被误诊。它们中的一些亚型是常染色体隐性遗传,因此在伊朗等近亲结婚现象普遍的国家很常见。在目前的研究工作中,确定了具有 EDS/OI/CL 表型重叠及其突变谱的伊朗患者队列。在此基础上,进行了硅分析,以预测更多可能的基因变异。利用网络服务器评估了伊朗患者中 EDS、OI 和 CL 变异的致病性。通过 String 数据库创建了蛋白质相互作用网络,并使用基于 Python 的库将其可视化。伊朗基因组数据库用于预测 EDS、OI 和 CL 综合征所有报告基因中的其他基因突变。在 EDS/OI/CL 重叠表型中,涉及 18 个基因中的 32 个变异。至少59%的患者来自近亲结婚家庭。相互作用分析表明,COL1A1、COL1A2、CRTAP、LEPRE1、PLOD1和ADAMTS2在EDS/OI/CL重叠表型的蛋白质网络中影响最大。通过分析 Iranome 数据库,发现了 46 个可能致病的 EDS、OI 和 CL 基因变异。EDS、OI和CL综合征的重叠表型需要通过基因检测(如全外显子组测序)来揭示各自的变异,这有助于更准确地诊断和更有效地管理疾病。特别是在伊朗等近亲结婚率较高的人群中,基因筛查在婚前和产前咨询中发挥着至关重要的作用,以防止这些罕见结缔组织疾病的传播。
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引用次数: 0
Osteogenesis imperfecta type XVII: expansion of the phenotype 成骨不全症 XVII 型:表型扩展
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-23 DOI: 10.1186/s43042-024-00475-9
Brooke M. Dunleavy, Alison J. Schildt, Caitlin Harrington, David A. Stevenson
Biallelic variants in SPARC are extremely rare, and have been reported in only a few cases of autosomal recessive osteogenesis imperfecta (OI) type XVII. Here, we describe an individual with a SPARC homozygous missense variant (c.787G > A; p.Glu263Lys) and expand on the phenotype. The proband had a history of multiple fractures, osteopenia, severe thoracolumbar levoscoliosis, rib fusion, global hypotonia, conductive hearing loss, and was non-ambulatory. Several of his features were similar to previously described cases, such as early neuromuscular concerns, scoliosis, long bone and vertebral compression fractures, and delayed motor milestones, suggesting these are consistent across SPARC-related osteogenesis imperfecta (OI). However, the proband sustained fractures at a younger age with a more severe course compared to most previous reports. He also had bony fusion of several ribs and hearing loss, which have not been reported in SPARC-related OI. Overall, the proband supports the current phenotype of SPARC-related OI, but also expands the phenotypic variability.
SPARC 的双唇变异极为罕见,仅在少数常染色体隐性成骨不全症(OI)XVII 型病例中有报道。在这里,我们描述了一个患有 SPARC 同源错义变异(c.787G > A; p.Glu263Lys)的个体,并对其表型进行了进一步的研究。该患者曾多次骨折、骨质疏松、严重的胸腰椎左侧骨质疏松症、肋骨融合、全身肌张力低下、传导性听力损失,并且不能行走。他的一些特征与之前描述的病例相似,如早期神经肌肉问题、脊柱侧弯、长骨和脊椎压缩性骨折以及运动发育迟缓,这表明这些特征在与SPARC相关的成骨不全症(OI)中是一致的。不过,与之前的大多数报告相比,该患者骨折的年龄更小,骨折的过程也更严重。他的几根肋骨也发生了骨融合,并伴有听力损失,而这些在SPARC相关成骨不全症中尚未见报道。总之,该病例支持SPARC相关OI的现有表型,但也扩大了表型的变异性。
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引用次数: 0
Association of p53 codon 72 polymorphism with weight and metabolic diseases in a Central Indian population 印度中部人群中 p53 密码子 72 多态性与体重和代谢疾病的关系
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-15 DOI: 10.1186/s43042-024-00472-y
Jessy Abraham, Deepak Mahapatra, Pratishtha Agrawal, Mary Jovita James
Metabolic dysregulation leading to diabetes is a major public health concern in India. While evidence has pointed to a role for genetic factors, there is still limited knowledge regarding the specific variants that play a part in this process. Recent studies have implicated Tumor protein, p53, a well-known tumor suppressor, in maintaining metabolic homeostasis in our body. Polymorphisms that can disrupt this function are thought to increase susceptibility to diabetic and prediabetic phenotypes like Metabolic syndrome (MetS). A common polymorphism at codon 72 (rs1042522) is associated with obesity and other metabolic disorders. However, its role may vary depending on the specific population and disease context. Our study aimed to evaluate whether the polymorphism at codon 72 of p53 (rs1042522) is associated with MetS and Diabetes, in a Central Indian population. A total of 66 individuals and 63 healthy controls, identified based on the National Cholesterol Education Program (NCEP)/Adult Treatment Panel-III (ATP-III) 2001 guidelines, were enrolled in the study. The carriers expressing mutant allele “G” for arginine at codon 72 had higher weight than those having wild-type allele “C” which codes for proline (p = 0.038). The majority of the subjects were heterozygous for p53 codon 72 polymorphism though the association was not statistically significant for either MetS or diabetes. Our findings suggest that p53 codon 72 (rs1042522) varaints may trigger metabolic dysfunction by impacting weight. The polymorphism appears to confer a heterozygous advantage, as individuals with a heterozygous genotype exhibited the highest susceptibility to metabolic disease. Although further studies are required, our results for the first time indicate that the p53 codon 72 (rs1042522) polymorphism could be considered a genetic marker to predict the increased susceptibility to diabetic and prediabetic phenotypes among Central Indian population.
导致糖尿病的代谢失调是印度的一个主要公共卫生问题。虽然有证据表明遗传因素在其中发挥了作用,但人们对在这一过程中发挥作用的特定变异体的了解仍然有限。最近的研究表明,肿瘤蛋白 p53(一种著名的肿瘤抑制因子)与维持体内代谢平衡有关。能破坏这一功能的多态性被认为会增加对糖尿病和糖尿病前期表型(如代谢综合征)的易感性。第 72 个密码子上的常见多态性(rs1042522)与肥胖和其他代谢紊乱有关。然而,其作用可能因特定人群和疾病背景而异。我们的研究旨在评估印度中部人群中 p53 第 72 个密码子上的多态性(rs1042522)是否与 MetS 和糖尿病有关。根据美国国家胆固醇教育计划(NCEP)/成人治疗小组-III(ATP-III)2001 年指南,共有 66 名个体和 63 名健康对照参加了研究。在第 72 个密码子上表达精氨酸突变等位基因 "G "的携带者的体重高于编码脯氨酸的野生型等位基因 "C "的携带者(P = 0.038)。大多数受试者是 p53 第 72 号密码子多态性的杂合子,但与 MetS 或糖尿病的相关性在统计学上并不显著。我们的研究结果表明,p53 第 72 个密码子(rs1042522)变异可能会通过影响体重引发代谢功能障碍。该多态性似乎具有杂合子优势,因为杂合子基因型的个体对代谢性疾病的易感性最高。虽然还需要进一步研究,但我们的研究结果首次表明,p53 第 72 个密码子(rs1042522)多态性可被视为一种遗传标记,用于预测中印度人群对糖尿病和糖尿病前期表型的易感性。
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引用次数: 0
MTHFR (C677T) polymorphism and its association with cytogenetic and clinical profile in individuals with primary amenorrhea 原发性闭经患者的 MTHFR (C677T) 多态性及其与细胞遗传学和临床概况的关系
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-08 DOI: 10.1186/s43042-023-00471-5
Priyanka M. Sanghavi, Divya Chandel
Abnormal folate metabolism is a risk factor for DNA hypomethylation and chromosomal nondisjunction. MTHFR is a candidate gene for folliculogenesis and ovarian development. In the present study, we aimed to investigate the distribution of the MTHFR C677T polymorphism in individuals with primary amenorrhea and it’s association with the cytogenetic and clinical profile. The MTHFR polymorphism (C677T) was checked in 45 females with PA and 45 control females (age-matched) with regular menstrual cycles using polymerase chain reaction-restriction fragment length polymorphism. We observed the CC genotype in 84.4% (n = 38) of the control group females and 48.9% (n = 22) of the case group females, CT genotype in 13.3% (n = 6) in the control group females and 24.4% (n = 11) in the case group females (p = 0.039; χ2 value 4.253; odd ratio 0.316, 95%CI 0.103–0.973) and TT genotype in 2.2% (n = 1) in the control group females and 26.7% (n = 12) in the case group females (p = 0.000266; χ2 value 13.294; odd ratio 0.048, 95%CI 0.006–0.397). Out of 45 case group females, 26 females showed 46,XX karyotype, 4 females showed male karyotype, 3 females showed pure Turner karyotype, 2 females were mosaic Turner and the rest of the females showed structural abnormalities like deletion, isochromosome and normal variants. The serum values revealed significantly lower levels (p = 0.032) of progesterone in the individuals with the TT genotype as compared to the CC genotype and the radiology profile showed a significant role of the MTHFR gene in ovarian development (p = 0.024). We suggest that the MTHFR polymorphism (C677T) might be responsible for the chromosomal nondisjunction in monosomy X females. It also influences the progesterone level and ovarian development, thus affecting folliculogenesis and the ovarian reserve responsible for primary amenorrhea.
叶酸代谢异常是 DNA 低甲基化和染色体非连接的危险因素。MTHFR 是卵泡生成和卵巢发育的候选基因。本研究旨在调查原发性闭经患者中 MTHFR C677T 多态性的分布及其与细胞遗传学和临床特征的关系。我们采用聚合酶链式反应-限制性片段长度多态性方法,对 45 名原发性闭经女性和 45 名月经周期规律的对照女性(年龄匹配)进行了 MTHFR 多态性(C677T)检测。我们观察到,84.4%(n = 38)的对照组女性和 48.9%(n = 22)的病例组女性为 CC 基因型,13.3%(n = 6)的对照组女性和 24.4%(n = 11)的病例组女性为 CT 基因型(P = 0.039;χ2值4.253;奇异比0.316,95%CI 0.103-0.973),对照组女性中TT基因型占2.2%(n = 1),病例组女性中TT基因型占26.7%(n = 12)(p = 0.000266;χ2值13.294;奇异比0.048,95%CI 0.006-0.397)。在 45 名病例组女性中,26 名女性表现为 46,XX 核型,4 名女性表现为男性核型,3 名女性表现为纯合特纳核型,2 名女性为镶嵌特纳核型,其余女性表现为结构异常,如缺失、同源染色体和正常变异。血清值显示,与 CC 基因型相比,TT 基因型个体的孕酮水平明显较低(p = 0.032),放射学特征显示 MTHFR 基因在卵巢发育中起着重要作用(p = 0.024)。我们认为,MTHFR 多态性(C677T)可能是导致单体 X 女性染色体不连接的原因。它还会影响孕酮水平和卵巢发育,从而影响卵泡生成和卵巢储备,导致原发性闭经。
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引用次数: 0
Diagnostic and prognostic value of single nucleotide polymorphisms in autophagy-related genes (ATG) among Egyptian patients with breast cancer disease 埃及乳腺癌患者自噬相关基因 (ATG) 单核苷酸多态性的诊断和预后价值
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-05 DOI: 10.1186/s43042-023-00470-6
Sara F. Saadawy, Ahmed Raafat, Walaa E. Omar
Autophagy-related genes (ATGs), associated with autophagy, contribute to the pathogenesis of many illnesses, including cancer. ATGs’ role in breast cancer (BC) is still under investigation. Therefore, the current study aimed to determine whether genetic variants in core ATGs correlate with BC prognosis and investigate their impact on protein plasma levels. This case–control study was carried out on 70 BC patients as well as 70 cancer-free controls in order to determine the association of these variants with BC risk. ATG10 (rs1864182) and ATG7 (rs1375206) polymorphisms were genotyped in whole blood samples using TaqMan SNP Genotyping Assays, and ATG7 and ATG10 levels in plasma were determined using ELISA. The results revealed that ATG7 (rs1375206) might contribute to BC, as patients with the GG genotype displayed a substantial association with BC (OR = 3.23, 95% CI 1.12–9.5) as well as a significant increase in ATG7 protein expression. For ATG7 rs1375206, genotypes GG was significantly associated with increased BC risk; carriers of the G allele frequently have a bad prognosis compared to carriers of the CC genotype (OR of mortality equals 3.01). Serum ATG 7 in the breast cancer patients’ group was significantly higher than that in the control group (p < 0.001). In contrast, carriers of the ATG10 (rs1864182) CC genotype were significant with a lower risk of BC (OR = 0.31, 95% CI 0.26–0.79) when compared with patients with AA genotype, while serum ATG 10 protein levels were decreased in patients carrying C allele (p < 0.05). Carriers of the C allele frequently have a good prognosis (OR of mortality equals 0.79) also the C allele were significantly less likely to have higher grade tumor (14.3% compared to 65.2% of A allele). Single gene polymorphisms (SNPs) within the ATG7 (rs1375206) and ATG 10 (rs1864182) are substantially correlated with BC among Egyptian females. Consequently, SNPs should be considered critical prognostic markers for distinguishing individuals with ATG7 (rs1375206) at elevated risk of developing BC as well as its progression from those with ATG 10 (rs1864182) at lower risk and the effect of these SNPs on its protein expression levels as ATG7 (rs1375206) polymorphism associated with decreased plasma ATG7 level, on the other hand, ATG 10 (rs1864182) polymorphism accompanied with increased ATG 10 plasma level.
自噬相关基因(ATGs)与自噬有关,是包括癌症在内的多种疾病的发病机理之一。ATGs在乳腺癌(BC)中的作用仍在研究中。因此,本研究旨在确定核心 ATGs 基因变异是否与乳腺癌预后相关,并调查其对蛋白血浆水平的影响。这项病例对照研究针对 70 名 BC 患者和 70 名无癌症对照者,以确定这些变异与 BC 风险的关联。使用TaqMan SNP基因分型测定法对全血样本中的ATG10(rs1864182)和ATG7(rs1375206)多态性进行基因分型,并使用ELISA测定血浆中的ATG7和ATG10水平。结果表明,ATG7(rs1375206)可能与BC有关,因为GG基因型患者与BC有很大关系(OR = 3.23,95% CI 1.12-9.5),且ATG7蛋白表达量显著增加。就 ATG7 rs1375206 而言,基因型 GG 与乳腺癌风险增加显著相关;与 CC 基因型携带者相比,G 等位基因携带者的预后往往较差(死亡率 OR 等于 3.01)。乳腺癌患者组的血清 ATG 7 明显高于对照组(P < 0.001)。相反,与 AA 基因型患者相比,ATG10(rs1864182)CC 基因型携带者罹患乳腺癌的风险较低(OR = 0.31,95% CI 0.26-0.79),而 C 等位基因携带者的血清 ATG 10 蛋白水平降低(P < 0.05)。C 等位基因携带者的预后通常较好(死亡率 OR 等于 0.79),而且 C 等位基因携带者患高级别肿瘤的几率明显较低(14.3%,而 A 等位基因携带者为 65.2%)。在埃及女性中,ATG7(rs1375206)和ATG10(rs1864182)的单基因多态性(SNPs)与乳腺癌密切相关。ATG7(rs1375206)多态性与血浆 ATG7 水平降低有关,而 ATG10(rs1864182)多态性则与 ATG 10 血浆水平升高有关。
{"title":"Diagnostic and prognostic value of single nucleotide polymorphisms in autophagy-related genes (ATG) among Egyptian patients with breast cancer disease","authors":"Sara F. Saadawy, Ahmed Raafat, Walaa E. Omar","doi":"10.1186/s43042-023-00470-6","DOIUrl":"https://doi.org/10.1186/s43042-023-00470-6","url":null,"abstract":"Autophagy-related genes (ATGs), associated with autophagy, contribute to the pathogenesis of many illnesses, including cancer. ATGs’ role in breast cancer (BC) is still under investigation. Therefore, the current study aimed to determine whether genetic variants in core ATGs correlate with BC prognosis and investigate their impact on protein plasma levels. This case–control study was carried out on 70 BC patients as well as 70 cancer-free controls in order to determine the association of these variants with BC risk. ATG10 (rs1864182) and ATG7 (rs1375206) polymorphisms were genotyped in whole blood samples using TaqMan SNP Genotyping Assays, and ATG7 and ATG10 levels in plasma were determined using ELISA. The results revealed that ATG7 (rs1375206) might contribute to BC, as patients with the GG genotype displayed a substantial association with BC (OR = 3.23, 95% CI 1.12–9.5) as well as a significant increase in ATG7 protein expression. For ATG7 rs1375206, genotypes GG was significantly associated with increased BC risk; carriers of the G allele frequently have a bad prognosis compared to carriers of the CC genotype (OR of mortality equals 3.01). Serum ATG 7 in the breast cancer patients’ group was significantly higher than that in the control group (p < 0.001). In contrast, carriers of the ATG10 (rs1864182) CC genotype were significant with a lower risk of BC (OR = 0.31, 95% CI 0.26–0.79) when compared with patients with AA genotype, while serum ATG 10 protein levels were decreased in patients carrying C allele (p < 0.05). Carriers of the C allele frequently have a good prognosis (OR of mortality equals 0.79) also the C allele were significantly less likely to have higher grade tumor (14.3% compared to 65.2% of A allele). Single gene polymorphisms (SNPs) within the ATG7 (rs1375206) and ATG 10 (rs1864182) are substantially correlated with BC among Egyptian females. Consequently, SNPs should be considered critical prognostic markers for distinguishing individuals with ATG7 (rs1375206) at elevated risk of developing BC as well as its progression from those with ATG 10 (rs1864182) at lower risk and the effect of these SNPs on its protein expression levels as ATG7 (rs1375206) polymorphism associated with decreased plasma ATG7 level, on the other hand, ATG 10 (rs1864182) polymorphism accompanied with increased ATG 10 plasma level.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"26 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374260","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
Pan-cancer analysis identified IGF2BP2 as a potential prognostic biomarker for multiple tumor types 泛癌症分析发现 IGF2BP2 是多种肿瘤类型的潜在预后生物标记物
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-04 DOI: 10.1186/s43042-023-00468-0
Hong-Lu Zhou, Dan-Dan Chen, Xiu-Ling Li
Insulin-like growth factor 2 (IGF2) mRNA-binding proteins 2 (IGF2BP2/IMP2), an RNA-binding protein encoded by the IGF2BP2 gene, exerts its influence across diverse pathological pathways. While accumulating evidence underscores the potential significance of IGF2BP2 in the tumorigenesis of specific cancers, a comprehensive pan-cancer investigation into its role remains absent. Consequently, we conducted an exhaustive exploration employing a multitude of databases to elucidate the plausible oncogenic implications of IGF2BP2. This encompassed a comprehensive scrutiny of its expression profiles, prognostic implications, association with cancer-associated fibroblast infiltration, biological functionality in distinct tumor contexts, and plausible correlations with drug sensitivities. Our findings showed that IGF2BP2 was highly expressed in some types of cancers, but presented at low levels in several cancer types. Furthermore, the role of IGF2BP2 in predicting prognosis exhibited a dichotomous interplay across varied cancer types. Remarkably, observations unveiled the cancer-associated fibroblast infiltration within specific tumors, notably encompassing breast invasive carcinoma of the luminal A subtype, kidney renal clear cell carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, and prostate adenocarcinoma, and thymoma. Intriguingly, gene enrichment analyses spotlighted the co-expression of IGF2BP2 with genes implicated in pivotal biological processes, including DNA replication and recombinational repair. Our investigation intricately unveils the potential of IGF2BP2 as a versatile prognostic biomarker across diverse tumor categories. This study bridges existing knowledge gaps and augments the understanding of IGF2BP2’s intricate involvement in tumorigenesis, underscoring its significance as a prospective avenue for therapeutic intervention.
胰岛素样生长因子 2(IGF2)mRNA 结合蛋白 2(IGF2BP2/IMP2)是一种由 IGF2BP2 基因编码的 RNA 结合蛋白,它在不同的病理途径中发挥着影响。尽管越来越多的证据强调了 IGF2BP2 在特定癌症的肿瘤发生过程中的潜在重要性,但对其作用的全面泛癌症调查仍然缺失。因此,我们利用大量数据库进行了详尽的探索,以阐明 IGF2BP2 的合理致癌影响。这包括对其表达谱、预后影响、与癌症相关成纤维细胞浸润的关联、在不同肿瘤环境中的生物学功能以及与药物敏感性的合理相关性的全面审查。我们的研究结果表明,IGF2BP2 在某些类型的癌症中表达量很高,但在几种癌症类型中的表达量却很低。此外,IGF2BP2 在不同癌症类型中预测预后的作用呈现出二分法的相互作用。值得注意的是,观察结果揭示了特定肿瘤中与癌症相关的成纤维细胞浸润,主要包括乳腺浸润性癌的管腔A亚型、肾脏肾透明细胞癌、卵巢浆液性囊腺癌、嗜铬细胞瘤和副神经节瘤、前列腺癌和胸腺瘤。耐人寻味的是,基因富集分析显示,IGF2BP2 与 DNA 复制和重组修复等关键生物过程中的相关基因共同表达。我们的研究巧妙地揭示了 IGF2BP2 作为多种肿瘤预后生物标志物的潜力。这项研究填补了现有的知识空白,加深了人们对 IGF2BP2 在肿瘤发生过程中错综复杂的参与关系的理解,并强调了其作为治疗干预的前瞻性途径的重要意义。
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引用次数: 0
Novel MTR compound-heterozygous mutations in a Chinese girl with HHcy due to methionine synthase deficiency, cblG: a case report 一名因蛋氨酸合成酶缺乏症(cblG)而患有HHcy的中国女孩的新型MTR复合杂合突变:病例报告
IF 1.3 Q4 GENETICS & HEREDITY Pub Date : 2024-01-03 DOI: 10.1186/s43042-023-00469-z
Juan Luo, Xiaohong Chen, Hongxi Guo, Peiwei Zhao, Hui Yao, Lifang Feng, Luhong Yang
The methylcobalamin deficiency G (cblG) disorder, a rare autosomal recessive disease, is attributed to mutations in the MTR gene, resulting in heightened homocysteine levels and reduced methionine and megaloblastic anemia levels. This disease is predominantly diagnosed using MTR gene variation analysis. Herein, we report the case of a 2.1-month-old Chinese girl with the cblG disorder with poor feeding, failure to thrive, and pancytopenia, esotropia, ocular nystagmus, and hypotonia. However, in order to determine the possible genetic cause of the disease, whole-exome sequencing was adopted and detected compound-heterozygous mutations in MTR gene. One was splicing site mutation c.1812 + 3A > G and the other was missense mutation c.2405G > A (p.A802G), which were likely disease-causing mutations (DM). Variant c.1812 + 3A > G has not been reported before in the literature. Our data elucidated the genetic etiology of the patient and enriched the known spectrum of mutations in the MTR gene worldwide, offering exhaustive and invaluable insights for early diagnosis and appropriate medication of the cblG disorder.
甲基钴胺素缺乏症 G(cblG)是一种罕见的常染色体隐性遗传病,其病因是 MTR 基因突变,导致同型半胱氨酸水平升高,蛋氨酸和巨幼红细胞贫血水平降低。该病主要通过 MTR 基因变异分析进行诊断。在此,我们报告了一例 2.1 个月大的中国女孩的病例,她患有 cblG 障碍,喂养不良,不能茁壮成长,并伴有泛发性眼球震颤、眼球后视、眼球震颤和肌张力低下。然而,为了确定该病可能的遗传原因,我们采用了全外显子组测序,并在 MTR 基因中检测到复合杂合突变。一个是剪接位点突变 c.1812 + 3A > G,另一个是错义突变 c.2405G > A (p.A802G),这两个突变很可能是致病突变(DM)。变异c.1812 + 3A > G在以前的文献中从未报道过。我们的数据阐明了该患者的遗传病因,丰富了全球已知的 MTR 基因突变谱,为 cblG 疾病的早期诊断和适当治疗提供了详尽而宝贵的见解。
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Egyptian Journal of Medical Human Genetics
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