Global Medical Genetics最新文献

{"title":"Genetically Predicted Iron Status Is a Causal Risk of Rheumatoid Arthritis: A Mendelian Randomization Study.","authors":"Boyuan Wu","doi":"10.1055/s-0044-1789259","DOIUrl":"10.1055/s-0044-1789259","url":null,"abstract":"<p><p><b>Background</b>  Current knowledge on iron's role in rheumatoid arthritis (RA) development is very limited, with studies yielding inconsistent findings. We conducted a two-sample Mendelian randomization study to assess the associations of iron status with the risk of RA. <b>Methods</b>  This study leveraged genetic data from a large genome-wide association study (GWAS) of 257,953 individuals to identify single nucleotide polymorphisms (SNPs) associated with iron status. We then analyzed these data in conjunction with summary-level data on RA from the IEU open GWAS project, which included 5,427 RA cases and 479,171 controls. An inverse-variance weighted method with random effects was employed, along with sensitivity analyses, to assess the relationship between iron status and RA risk. <b>Results</b>  Genetic predisposition to high ferritin and serum iron status was causally associated with lower odds of RA. Ferritin had an odds ratio (OR) of 0.997 (95% confidence interval [CI]: 0.995-0.997; <i>p</i>  = 0.010), indicating that a one-unit increase in ferritin is associated with a 0.3% decrease in the odds of RA. Similarly, serum iron had an OR of 0.997 (95% CI: 0.995-0.999; <i>p</i>  = 0.014). However, MR analyses found no significant causal associations between total iron-binding capacity (OR = 1.0, 95% CI: 0.999-1.002; <i>p</i>  = 0.592) or transferrin saturation percentage (OR = 0.998, 95% CI: 0.996-1.000; <i>p</i>  = 0.080) and risk of developing RA. <b>Conclusions</b>  This study suggests that individuals with genes linked to higher iron levels may have a lower risk of developing RA. Our findings indicate that the total amount of iron in the body, rather than how it is distributed, might be more important for RA. This raises the intriguing possibility that iron supplementation could be a preventative strategy, but further research is necessary.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"270-277"},"PeriodicalIF":1.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"16S rRNA Sequencing Reveals Alterations of Gut Bacteria in Hirschsprung-Associated Enterocolitis.","authors":"Hao Shi, Yong She, Wu Mao, Yi Xiang, Lu Xu, Sanjun Yin, Qi Zhao","doi":"10.1055/s-0044-1789237","DOIUrl":"10.1055/s-0044-1789237","url":null,"abstract":"<p><p>Hirschsprung-associated enterocolitis (HAEC) stands as most common and serious complication of Hirschsprung's disease. Variations in the microbiota composition may account for the differences observed between HAEC and healthy individuals, offering crucial insights into the disease's pathogenesis. Here, we performed a study to changes in the gut microbiome using 16sRNA amplicon sequencing in a cohort of HAEC patients ( <i>n</i>  = 16) and healthy controls ( <i>n</i>  = 14). Our result revealed a significant disparity in beta diversity between the two groups. Following correction for false discovery rate, a rank-sum test at the genus level indicated a notable decrease in the relative abundance of <i>Bifidobacterium</i> , <i>Lactobacillus</i> , and <i>Veillonella</i> , whereas the <i>Enterococcus</i> genus exhibited a substantial increase in HAEC, a finding further supported by additional linear discriminant analysis effect size analysis. Functional analysis showed that putative transport and catabolism, digestive system, and metabolism of cofactors and vitamins were proved to be some abundant KOs (Kyoto Encyclopedia of Genes and Genomes [KEGG] orthologs) in healthy group, whereas infectious disease, membrane transport, and carbohydrate metabolism were the three KOs with the higher abundance in the HAEC group. Our data increased our insight into the HAEC, which may shed further light on HAEC pathogenesis. Our study firstly demonstrated the difference between fecal microbiota of HAEC patients and healthy individuals, which made a step forward in the understanding of the pathophysiology of HAEC.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"263-269"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.","authors":"Lei Cao, Wencong Tian, Yongjie Zhao, Peng Song, Jia Zhao, Chuntao Wang, Yanhong Liu, Hong Fang, Xingqiang Liu","doi":"10.1055/s-0044-1789204","DOIUrl":"10.1055/s-0044-1789204","url":null,"abstract":"<p><p>Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine-threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named \"quadruple WT\" GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"251-262"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AQP4-AS1 Can Regulate the Expression of Ferroptosis-Related Regulator ALOX15 through Competitive Binding with miR-4476 in Lung Adenocarcinoma.","authors":"Lin Du, Geng Xu, Xiuqiang Zhang, Zhiwei Zhang, Yang Yang, Hongsheng Teng, Tao Yang","doi":"10.1055/s-0044-1789199","DOIUrl":"10.1055/s-0044-1789199","url":null,"abstract":"<p><p><b>Background</b>  The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment. <b>Methods</b>  After bioinformatics analysis, we contained one ferroptosis-related gene (FRG), namely ALOX15. MicroRNAs (miRNAs) and long noncoding RNAs were predicted by miRWalk. Furthermore, we constructed overexpressed LUAD cell lines. Real-time quantitative polymerase chain reaction and western blot were used to determine the expression of mRNA and protein, respectively. Cell Counting Kit-8 (CCK-8) and EdU assay were used to detect the cell proliferation. Double luciferase assay was used to detect the binding relationship between AQP4-AS1 and miR-4464. <b>Results</b>  ALOX15 was the most significantly downregulated FRG compared with normal tissues. Furthermore, protein-protein interaction network analysis indicated that the AQP4-AS1-miR-4476-ALOX15 regulatory axis might be involved in the occurrence and development of LUAD and there might be direct interaction between AQP4-AS1 and miR-4476, and miR-4476 and ALOX15. Furthermore, AQP4-AS1 and ALOX15 were significantly downregulated in the LUAD tissue and cell lines, whereas miR-4476 showed the opposite results ( <i>p</i>  < 0.001). AQP4-AS1 overexpression improved the ALOX15 expression in LUAD cell lines. CCK-8 and EdU assay revealed that overexpression of AQP4-AS1 and ALOX15 inhibited the LUAD cell proliferation. Double luciferase assay results indicated that there was a combination between AQP4-AS1 and miRNA-4476. In addition, we found that overexpressed AQP4-AS1 activates the ferroptosis in LUAD cell lines. <b>Conclusions</b>  AQP4-AS1 can regulate the expression of ALOX15 through competitive binding with miR-4476, further activate ferroptosis and inhibit the proliferation of LUAD cells.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"241-250"},"PeriodicalIF":1.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing Cell-free Genomic DNA in Spent Culture Media: Noninvasive Insight into the Blastocysts.","authors":"Siddhartha Shankar Layek, Shrushti Kanani, Shilpa Doultani, Tejas Gohil, Sanket Patil, Ananthasayanam Sudhakar, Kathan Banubhai Raval, Karuppanasamy Kuppusamy, Sanjay Gorani, Sudharson Raj, Rafiya Sangameshwari, Himali Jadeja, Mini Mol P","doi":"10.1055/s-0044-1788260","DOIUrl":"10.1055/s-0044-1788260","url":null,"abstract":"<p><p>A commonly accepted standard protocol for noninvasive techniques for the genetic evaluation of an embryo remains elusive due to inconclusiveness regarding the volume of spent media to be acquired and the possibility of acquiring the same for subsequent analysis. Single embryo culture is imperative for standardizing noninvasive preimplantation testing using cell-free DNA (cf-DNA) released by individual developing embryos. This study aims to compare the development dynamics of single-drop embryonic culture against with group embryonic culture to establish a standardized protocol for noninvasive Preimplantation Genetic Testing (PGT) in bovine. A total of 239 cumulus-oocyte complexes were aspirated and subjected to in vitro maturation and fertilization. Among these, 120 embryos of day 3 were transferred to single-drop culture until the blastocyst stage. The single-drop culture drops were prepared using microdrops of 30 μL. At the blastocyst stage, spent media from all single-drop embryos were utilized for extracting cell-free genomic DNA to standardize the protocol. The blastocyst rate indicates no significant difference between the two culture methods, suggesting that single-drop culture is suitable for the process. Additionally, the extracted spent media yielded sufficient quantities of cf-DNA, supporting its potential use for PGT ( <i>p</i>  < 0.05). These findings support the hypothesis that single-drop embryo culture is a viable method for cf-DNA extraction and confirm the potential of using DNA fragments from spent media as a reliable source for noninvasive PGT.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"227-232"},"PeriodicalIF":1.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABO Blood Type and Urinary Bladder Cancer: Phenotype, Genotype, Allelic Association with a Clinical or Histological Stage and Recurrence Rate.","authors":"Ivan Milas, Željko Kaštelan, Jószef Petrik, Jasna Bingulac-Popović, Bojan Čikić, Andrej Šribar, Irena Jukić","doi":"10.1055/s-0044-1788614","DOIUrl":"10.1055/s-0044-1788614","url":null,"abstract":"<p><p><b>Background</b>  Previous research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. <b>Aim</b>  To investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. <b>Materials and Methods</b>  In the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence-specific primers. We compared ABO phenotypes, genotypes, and alleles between patients and the healthy controls and investigated their distribution according to the clinical and histological stage and recurrence rate. <b>Results</b>  No statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 ( <i>p</i>  < 0.001), A1 ( <i>p</i>  < 0.001), and B ( <i>p</i>  = 0.013), and a lower proportion of metastatic disease in A2 (0%, <i>p</i>  = 0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, <i>p</i>  < 0.001), A1 (70.1%, <i>p</i>  = 0.019), of nonmuscle invasive tumors in patients with O1 (55.1%, <i>p</i>  < 0.001), O2 (100%, <i>p</i>  = 0.045), and recurrent tumors in patients with O1 (70.2%, <i>p</i>  < 0.001) and A1 (74.2%, <i>p</i>  = 0.007) alleles. <b>Conclusion</b>  We did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage, and recurrence rate, respectively.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"233-240"},"PeriodicalIF":1.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Innovation Research with Clinical Application: Clinical Trials at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences.","authors":"Xiaochen Wang, Lijun Liu","doi":"10.1055/s-0044-1788572","DOIUrl":"10.1055/s-0044-1788572","url":null,"abstract":"","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"225-226"},"PeriodicalIF":1.5,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"46 XX Ovotesticular Disorder of Sex Development with Gonadotropin-Releasing Hormone Receptor, Autosomal Recessive Heterozygous Missense Mutation and Autosomal Dominant Heterozygous Missense Mutation of the <i>PROKR2</i> Gene: A Case Report.","authors":"Francesca Peranzoni, Roberto De Castro, Emilio Merlini, Yen Le Nguyen","doi":"10.1055/s-0044-1788060","DOIUrl":"10.1055/s-0044-1788060","url":null,"abstract":"<p><p>True hermaphroditism is a disorder of sex development (DSD), accounting for less than 5% of all DSD cases, defined by the simultaneous presence of testicular tissue and ovarian tissue in the same individual. In the reported case, the patient presented two genetic mutations involved in the pathogenic pathway of the DSD condition associated with the clinical features of Kallmann syndrome (KS), a developmental disease that associates hypogonadotropic hypogonadism (HH), due to gonadotropin-releasing hormone deficiency, and anosmia, related to the absence or hypoplasia of the olfactory bulbs. Given the variable degree of hyposmia in KS, the distinction between KS and normosmic idiopathic HH is currently unclear, especially as HH patients do not always undergo detailed olfactory testing. This syndrome is very rare, with an estimated prevalence of 1:80,000 in males and 1:40,000 in females. This is the only case report concerning a patient with 46 XX true hermaphroditism affected by HH and digenic inheritance of Kallmann syndrome.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"220-224"},"PeriodicalIF":1.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.","authors":"Shiyuan Wang, Jun Li, Ying Li, Xiaoming Liu, Lixian Chang, Beibei Zhao, Li Zhang, Yao Zou, Min Ruan, Xiaofan Zhu","doi":"10.1055/s-0044-1788043","DOIUrl":"10.1055/s-0044-1788043","url":null,"abstract":"<p><p>Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"214-219"},"PeriodicalIF":1.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Alarming Situation of Highly Pathogenic Avian Influenza Viruses in 2019-2023.","authors":"Zhiwei Zhang, Zhao Lei","doi":"10.1055/s-0044-1788039","DOIUrl":"10.1055/s-0044-1788039","url":null,"abstract":"<p><p>Avian influenza viruses (AIVs) have the potential to cause severe illness in wild birds, domestic poultry, and humans. The ongoing circulation of highly pathogenic avian influenza viruses (HPAIVs) has presented significant challenges to global poultry industry and public health in recent years. This study aimed to elucidate the circulation of HPAIVs during 2019 to 2023. Specifically, we assess the alarming global spread and continuous evolution of HPAIVs. Moreover, we discuss their transmission and prevention strategies to provide valuable references for future prevention and control measures against AIVs.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"200-213"},"PeriodicalIF":1.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}