Genetic testing and molecular biomarkers最新文献

{"title":"Targeted Next-Generation Sequencing Analysis Reveals a Novel Genetic Variant in <i>MYO6</i> Gene in an Indian Family with Postlingual Nonsyndromic Hearing Loss.","authors":"Ruchika Raghuvanshi, Khirod Chandra Panda, Chinmay Sundar Ray, Puppala Venkat Ramchander","doi":"10.1089/gtmb.2023.0747","DOIUrl":"10.1089/gtmb.2023.0747","url":null,"abstract":"<p><p><b><i>Background:</i></b> Hereditary nonsyndromic hearing loss (NSHL) is an extremely heterogeneous disorder, both genetically and clinically. Myosin VI (<i>MYO6</i>) pathogenic variations have been reported to cause both prelingual and postlingual forms of NSHL. Postlingual autosomal dominant cases are often overlooked for genetic etiology in clinical setups. In this study, we used next-generation sequencing (NGS)-based targeted deafness gene panel assay to identify the cause of postlingual hearing loss in an Indian family. <b><i>Methods:</i></b> The proband and his father from a multigenerational Indian family affected by postlingual hearing loss were examined via targeted capture of 129 deafness genes, after excluding gap junction protein beta 2 (<i>GJB2</i>) pathogenic variants by Sanger sequencing. NGS data analysis and co-segregation of the candidate variants in the family were carried out. The variant effect was predicted by <i>in silico</i> tools and interpreted following American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. <b><i>Results:</i></b> A novel heterozygous transversion c.3225T>G, p.(Tyr1075*) in <i>MYO6</i> gene was identified as the disease-causing variant in this family. This stop-gained variant is predicted to form a truncated myosin VI protein, which is devoid of crucial cargo-binding domain. PCR-RFLP screening in 200 NSHL cases and 200 normal-hearing controls showed the absence of this variant indicating its <i>de novo</i> nature in the population. Furthermore, we reviewed <i>MYO6</i> variants reported from various populations to date. <b><i>Conclusions:</i></b> To the best of our knowledge, this is the first family with <i>MYO6</i>-associated hearing loss from an Indian population. The study also highlights the importance of deafness gene panels in molecular diagnosis of <i>GJB2</i>-negative pedigrees, contributing to genetic counseling in the affected families.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"328-336"},"PeriodicalIF":1.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633068","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":"Influence of TPMT and NUDT15 Genetic Polymorphisms on Mercaptopurine Pharmacokinetics in Healthy Volunteers.","authors":"Qihui Kong, Qiqi Zhang, Di Chen, Jinfang Lou, Jian Zhu, Mingjing Chen, Ting Li","doi":"10.1089/gtmb.2023.0605","DOIUrl":"10.1089/gtmb.2023.0605","url":null,"abstract":"<p><p><b><i>Aims:</i></b> This study aimed to investigate the impact of genetic polymorphisms of thiopurine methyltransferase (TPMT) and NUDT15 on pharmacokinetics profile of mercaptopurine in healthy adults in China. <b><i>Methods:</i></b> Blood samples were obtained from 45 healthy adult volunteers who were administered azathioprine. Genomic DNA was extracted and sequenced for TPMT and NUDT15. The plasma concentrations of 6-mercaptopurine (6-MP) were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Finally, pharmacokinetic parameters were calculated based on the time-concentration curve. <b><i>Results:</i></b> Among the 45 healthy adult volunteers enrolled in the study, two TPMT allelic variants and three NUDT15 allelic variants were detected. In total, six genotypes were identified, including <i>TPMT*1/*1&NUDT15*1/*1</i>, <i>TPMT*1/*1&NUDT15*1/*2</i>, <i>TPMT*1/*1&NUDT15*1/*9</i>, <i>TPMT*1/*1&NUDT15*2/*5, TPMT*1/*6&NUDT15*1/*2,</i> and <i>TPMT*1/*3&NUDT15*1/*2</i>. The results indicated that Area Under Curve (AUC) of 6-MP in volunteers with TPMT*1/*3&NUDT15*1/*2 and TPMT*1/*6&NUDT15*1/*2 were 1.57-1.62-fold higher than in individuals carrying the wild type (TPMT*1/*1&NUDT15*1/*1). Compared with wild type, the half-life (T_1/2) of <i>TPMT*1/*6&NUDT15*1/*2</i> was extended by 1.98 times, whereas T_1/2 of <i>TPMT*1/*3&NUDT15*1/*2</i> decreased by 67%. The maximum concentration (C_max) of <i>TPMT*1/*3&NUDT15*1/*2</i> increased significantly by 2.15-fold, whereas the corresponding clearance (CL/F) decreased significantly by 58.75%. <b><i>Conclusion:</i></b> The findings of this study corroborate the notion that various genotypes of TPMT and NUDT15 can impact the pharmacokinetics of mercaptopurine, potentially offering foundational insights for personalized mercaptopurine therapy.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"322-327"},"PeriodicalIF":1.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859528","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":"Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.","authors":"Zhonglin Liu, Chunyan Wang, Feng Ni, Tingshu Li, Fenglian Yang, Han Wei, Tengyan Li, Changhui Huang, Junli Wang, Binbin Wang","doi":"10.1089/gtmb.2023.0263","DOIUrl":"10.1089/gtmb.2023.0263","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes. <b><i>Methods:</i></b> A Chinese infertile man with MMAF and PCD was enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify potential causative genes and mutations. <b><i>Results:</i></b> A novel homozygous missense mutation (c.1450G>A; p.E484K) of <i>CCDC40</i> was finally identified and Sanger sequencing confirmed that the patient carried the homozygous mutation, which was inherited from his parents. We reported the first homozygous missense <i>CCDC40</i> mutation in infertile men with MMAF but had other milder PCD symptoms. <b><i>Conclusion:</i></b> Our findings not only broaden the disease-causing mutation spectrum of <i>CCDC40</i> but also provide new insight into the correlation between <i>CCDC40</i> mutations and MMAF.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"337-341"},"PeriodicalIF":1.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247663","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":"<i>HFE</i> and Non-<i>HFE</i> Hereditary Hemochromatosis Based on Screening of 854 Individuals: 12 Years of an Iranian Experience.","authors":"Razieh Zarifian Yeganeh, Masoumeh Akbari Kelishomi, Atiyeh Ahmadpour Jenaghard, Banafsheh Salmani, Zohreh Vahidi, Mina Makvand, Maryam Azad, Mahdieh Kooshki, Yassin Bouraqi, Azita Azarkeivan, Hossein Najmabadi, Maryam Neishabury","doi":"10.1089/gtmb.2023.0764","DOIUrl":"10.1089/gtmb.2023.0764","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> The genetics of hereditary hemochromatosis (HH) is understudied in Iran. Here, we report the result of genetic screening of 854 individuals, referred as \"suspected cases of HH,\" to a diagnostic laboratory in Iran over a 12-year period. <b><i>Materials and Methods:</i></b> From 2011 to 2012, 121 cases were screened for HH using Sanger sequencing of <i>HFE</i> exons. After 2012, this method was replaced by a commercial reverse hybridization assay (RHA) targeting 18 variants in the <i>HFE</i>, <i>TFR2</i>, and <i>FPN1(SLC40A1)</i> genes and 733 cases were screened using this method. <b><i>Results:</i></b> From the total studied population, HH was confirmed by genetic diagnosis in only seven cases (0.82%): two homozygotes for <i>HFE</i>:C282Y and five homozygotes for <i>TFR2</i>:AVAQ 594-597 deletion. In 254 cases (29.7%), H63D, C282Y, S65C, and four other <i>HFE</i> variants not targeted by RHA were identified. Although the resulting genotypes in the latter cases did not confirm HH, some of them were known modifying factors of iron overload or could cause HH in combination with a possibly undetected variant. No variant was detected in 593 cases (69.4%). <b><i>Conclusion:</i></b> This study showed that the spectrum of genetic variants of HH in the Iranian population includes <i>HFE</i> and <i>TFR2</i> variants. However, HH was not confirmed in the majority (99.2%) of suspected cases. This could be explained by limitations of our genetic diagnostics and possible inaccuracies in clinical suspicion of HH. A cooperative clinical and genetic investigation is proposed as a solution to this issue.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"289-296"},"PeriodicalIF":1.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563148","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":"Genetic Polymorphism of Interleukin-6 in Asymptomatic and ICU-Admitted COVID-19 Patients in Sulaymaniyah Province, Kurdistan Region of Iraq.","authors":"Peshnyar M A Rashid, Gaza F Salih","doi":"10.1089/gtmb.2023.0304","DOIUrl":"10.1089/gtmb.2023.0304","url":null,"abstract":"<p><p><b><i>Background:</i></b> The global pandemic of Coronavirus Disease 2019 (COVID-19) has resulted in significant fatality rates. Clinical outcomes for affected individuals range from being asymptomatic to severe illnesses requiring intensive care unit (ICU) admission. Among the various factors contributing to the variation in clinical outcomes, host genetics play a prominent role. Interleukin-6 (IL6), a key player in immune responses, has been identified as having a crucial impact on viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, certain variations known as single nucleotide polymorphisms (SNPs) in the IL6 promoter region have been found to significantly influence IL6 expression and the severity of viral infections. <b><i>Materials and Methods:</i></b> To explore the relationship between these genetic variations and COVID-19 in asymptomatic and ICU-admitted Kurdish patients, genetic sequencing was performed to determine the genotypes of nine IL6 SNPs. <b><i>Results:</i></b> The study findings revealed that although the proportion of the GG genotype of rs1800795 was slightly higher in asymptomatic COVID-19 cases, the difference was not statistically significant (chi2 = 2.666, <i>p</i> = 0.236). Notably, Kurdish patients displayed a uniform genetic makeup (monomorphic) for the dominant alleles of rs2069830 (C), rs142759801 (C), rs2069857 (C), rs2069829 (G), rs2234683 (G), rs13447446 (T), rs527770772 (C), and rs13447445 (C). Furthermore, patients carrying the haplotype GCGGCTCCC were found to have a 0.481-fold higher likelihood of being asymptomatic with COVID-19 (<i>p</i> = 0.016, OR = 0.481). <b><i>Conclusions:</i></b> This study demonstrates that the rs1800795 SNP is not statistically associated with COVID-19 at the genotype level. However, the presence of the dominant G allele of rs1800795 in the haplotype was found to be statistically associated with asymptomatic COVID-19 patients.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"297-303"},"PeriodicalIF":1.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891805","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 Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans.","authors":"Ting Huang, Xianpeng Zhang, Qiang Li, Xin Li, Jie Yao, Jia Song, Ying Chen, Liping Ye, Chunshan Li, Pingcuo Xiran, Youfeng Wen","doi":"10.1089/gtmb.2023.0546","DOIUrl":"10.1089/gtmb.2023.0546","url":null,"abstract":"<p><p><b><i>Background:</i></b> A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. <b><i>Methods:</i></b> Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. <b><i>Result:</i></b> Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. <b><i>Conclusion:</i></b> Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"28 7","pages":"267-274"},"PeriodicalIF":1.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733939","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 of <i>ACTN4</i> Gene Mutation with Primary Nephrotic Syndrome in Children in Guangxi Autonomous Region, China.","authors":"Shan Cao, Dan Wang, Lixiao Liu, Junyan Yao, Lingli Wang, Yang Liao, Jinfeng Zhang, Jie Zhao, Ying Huang, Zhiyan Hao","doi":"10.1089/gtmb.2023.0567","DOIUrl":"10.1089/gtmb.2023.0567","url":null,"abstract":"<p><p><b><i>Objective:</i></b> To investigate the association between <i>ACTN4</i> gene mutation and primary nephrotic syndrome (PNS) in children in Guangxi Autonomous Region, China. <b><i>Methods:</i></b> The high-throughput sequencing technology was used to sequence <i>ACTN4</i> gene in 155 children with PNS in Guangxi Autonomous Region in China, with 98 healthy children serving as controls. Twenty-three exon-specific capture probes targeting <i>ACTN4</i> were designed and used to hybridize with the genomic DNA library. The targeted genomic region DNA fragments were enriched and sequenced. The protein levels of <i>ACTN4</i> in both case and control groups were quantified using ELISA method. <b><i>Results:</i></b> Bioinformatics analysis revealed five unique <i>ACTN4</i> mutations exclusively in patients with PNS, including c.1516G>A (p.G506S) on one exon in 2 patients, c.1442 + 10G>A at the splice site in 1 patient, c.1649A>G (p.D550G) on exon in 1 patient, c.2191-4G>A at the cleavage site in 2 patients, and c.2315C>T (p.A772V) on one exon in 1 patient. The c.1649A>G (p.D550G) and c.2315C>T (p.A772V) were identified from the same patient. Notably, c.1649A>G (p.D550G) represents a novel mutation in <i>ACTN4</i>. In addition, three other <i>ACTN4</i> polymorphisms occurred in both case and control groups, including c.162 + 6C>T (1 patient in case group and 2 patients in control group), c.572 + 11G>A (1 patient in case group and 2 patients in control group), and c.2191-5C>T (4 patients in the case group and 3 patients in control group). The serum ACTN4 concentration in the case group was markedly higher, averaging 544.7 ng/mL (range: 264.6-952.6 ng/mL), compared with 241.20 ng/mL (range: 110.75-542.35 ng/mL) in the control group. <b><i>Conclusion:</i></b> Five <i>ACTN4</i> polymorphisms were identified among children with PNS in Guangxi Autonomous Region, China, including the novel mutation c.1649A>G. The lower serum levels of α-actinin-4 in the case group suggest that this protein might play a protective role in PNS.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"281-288"},"PeriodicalIF":1.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476396","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 Evaluation of the Genetic Variation Types of the <i>Uridine Diphosphate Glucuronosyl Transferase 1A1</i> Gene by Next-Generation Sequencing and Their Effects on Bilirubin Levels in Obese Children.","authors":"Merve Aslantas, Onder Kilicaslan, Recep Eröz, Kenan Kocabay","doi":"10.1089/gtmb.2023.0365","DOIUrl":"10.1089/gtmb.2023.0365","url":null,"abstract":"<p><p><b><i>Background and Objectives:</i></b> Obesity is a major nutritional problem with an increasing prevalence among children and adolescents. The <i>uridine-diphosphate-glucuronosyl-transferase1A1</i> (<i>UGT1A1</i>) gene encodes the UDP-glucuronosyl transferase enzyme, converting the toxic form of bilirubin to a soluble, nontoxic form. There are yet to be studies on the evaluation of the <i>UGT1A1</i> variant types detected by next-generation sequencing (NGS) and their effects on bilirubin levels in nonsyndromic obese children. <b><i>Methods:</i></b> Forty-five children with body mass index (BMI) >95 percentile (p) constituted the obesity group and fourteen healthy children with BMI <85p constituted the control group. Anthropometric, clinical features, and biochemical parameters were evaluated. Furthermore, the <i>UGT1A1</i> gene was sequenced by NGS. <b><i>Results:</i></b> The obese patients had lower total, direct, and indirect bilirubin levels (<i>p</i> = 0.422, 0.026, and 0.568, respectively). In addition, obese patients had more genetic variations in the <i>UGT1A1</i> gene compared with the control group (62.2% and 50%, respectively). We found that children with variations had higher total direct and indirect bilirubin levels compared with those without variation (<i>p</i> = 0.016, 0.028, and 0.015, respectively). Children diagnosed with obesity in the first two years of their life had fewer genetic variations and lower total bilirubin levels (<i>p</i> = 0.000 and 0.013, respectively). <b><i>Conclusions:</i></b> It is assumed that bilirubin can be protective against many chronic diseases. Although bilirubin levels are found to be lower in obese children compared with the control group, some variations in the <i>UGT1A1</i> gene may be supported by raising bilirubin. We suggest that high bilirubin levels caused by those <i>UGT1A1</i> variations may be protective against obesity and its many negative effects.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"275-280"},"PeriodicalIF":1.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446044","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":"Aberrant Super-Enhancer Landscape in Enzalutamide-Resistant Prostate Cancer Cells.","authors":"Chao Cai, Qinwei Liu, Haoran Shan, Chuanfan Zhong, Guidong Chen, Zhouda Cai, Yu Zheng, Jianming Lu, Jiaojiao Tang, Zhuoyuan Lin","doi":"10.1089/gtmb.2023.0280","DOIUrl":"10.1089/gtmb.2023.0280","url":null,"abstract":"<p><p><b><i>Background:</i></b> Castration-resistant prostate cancer (CRPC), which has developed resistance to next-generation antiandrogens, such as enzalutamide (Enz), is a lethal disease. Furthermore, transcriptional regulation by super enhancers (SEs) is crucial for the growth and spread of prostate cancer, as well as drug resistance. The functions of SEs, a significant class of noncoding DNA cis-regulatory elements, have been the subject of numerous recent studies in the field of cancer research. <b><i>Materials and Methods:</i></b> The goal of this research was to identify SEs associated with Enz resistance in C4-2B cells using chromatin immunoprecipitation sequencing and cleavage under targets and tagmentation (CUT&Tag). Using HOMER analysis to predict protein/gene-binding motifs, we identified master transcription factors (TFs) that may bind to SE sites. Using small interfering RNA, WST-1 assays, and qRT-PCR, we then confirmed the associations between TFs of SEs and Enz resistance. <b><i>Results:</i></b> A total of 999 SEs were screened from C4-2B EnzR cells in total. Incorporating analysis with RNA-seq data revealed 41 SEs to be strongly associated with the promotion of Enz resistance. In addition, we finally predicted that master TFs bind to SE-binding regions. Subsequently, we selected zinc finger protein 467 (ZFP467) and SMAD family member 3 to confirm the functional connections of master TFs with Enz resistance through SEs (ZNF467). <b><i>Conclusions:</i></b> In this study, SMAD3 and ZNF467 were found to be closely related to Enz-resistant CRPC. Our research uncovered a sizable group of SEs linked to Enz resistance in prostate cancer, dissected the mechanisms underlying SE Enz resistance, and shed light on potential clinical uses for SEs.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"243-256"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896212","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 of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Variants, Their Serum Levels, and Activities with Aortic Valve Calcification (AVC) in a Population from Western Iran.","authors":"Reza Heidari Moghadam, Fatemeh Babajani, Afshin Karami, Daniel Elieh-Ali-Komi, Faeghe Hoseini, Nahid Salehi, Saeed Elahirad, Ehsan Mohammadi-Noori, Hossein Mohammadi, Amir Kiani","doi":"10.1089/gtmb.2023.0370","DOIUrl":"10.1089/gtmb.2023.0370","url":null,"abstract":"<p><p><b><i>Background:</i></b> Matrix metalloproteinase (MMP) enzyme gene polymorphisms MMP-2-1575G/A and MMP-9-1562C/T promoter polymorphism, their serum levels, and activity are associated with aortic valve calcification (AVC). <b><i>Materials and Methods:</i></b> The synergistic link between the risk of AVC and the alleles T and A of MMP-9 and MMP-2 was investigated, respectively. Ninety-two cases with AVC and 92 healthy individuals from the west of Iran were included, and MMP- 2-1575G/A and MMP-9-1562C/T promoter polymorphisms were detected using PCR-RFLP. The serum levels and activity of MMP-2 and -9 were assessed using ELISA and gelatin zymography methods, respectively. In addition, serum biochemical markers, including FBS, urea and creatinine, cholesterol, triglyceride, HDL, LDL, calcium, phosphorus, and blood pressure: systolic blood pressure and diastolic blood pressure were measured. <b><i>Results:</i></b> Heart valve calcification disease was associated with a comparatively higher frequency of the A allele of the MMP2-1575 variation (<i>p</i> = 0.002). In addition, the frequency of T allele of the MMP9-1562 variant was higher than the control group (<i>p</i> = 0.007). <b><i>Conclusion:</i></b> MMP-2 and MMP-9 serum levels and activities were observed to be considerably higher in the experimental group than in the control group (<i>p</i> < 0.001). Patients are more susceptible to cardiovascular disease than the control group due to elevated serum levels and activity of MMP-2 and MMP-9.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"223-232"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853078","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}