Genetics research最新文献

Background: Coagulation system abnormalities contribute to clinical manifestations in preeclampsia (PE), but the mechanisms of coagulation and fibrinolysis in PE are unclear. Methods: We utilized the Gene Expression Omnibus (GEO) database to obtain the GSE10588 training set and GSE54618 validation set. From GeneCards, we extracted 514 coagulation and fibrinolysis-related genes (CFRGs). Differential expression analysis identified 1521 DEGs in the GSE10588 training set. WGCNA revealed the salmon module (778 genes) as the key module. LASSO and SVM-RFE methods identified four biomarkers (CYP19A1, C1QBP, GHR, and PSMA3) for a diagnostic model. GSEA was performed on the biomarkers. Immune cell infiltration and therapeutic agents for the biomarkers were analyzed. A circRNA-miRNA-mRNA network was constructed. Results: The salmon module showed the highest correlation with PE and normal samples. The diagnostic model comprised CYP19A1, C1QBP, GHR, and PSMA3. Immune cell analysis revealed significant differences, including type 2 T helper cells and regulatory T cells. C1QBP correlated positively with effector memory CD4 T cells, while PSMA3 had a negative correlation with CD56dim natural killer cells. Sixty-one potential therapeutic agents were predicted, as well as n circRNA-miRNA-mRNA network composed of 73 nodes and 88 edges. Conclusion: Our bioinformatic analysis resulted in a diagnostic model (CYP19A1, C1QBP, GHR, and PSMA3) for PE related to coagulation and fibrinolysis. We also conducted immune microenvironment and drug sensitivity analyses, providing insights into PE diagnosis and treatment.

Background: Hypospadias is one of the most common male congenital external genital malformation anomalies with unclear and multifactorial etiology. Our study aims to investigate whether IRX6 rs6499755 and HAAO rs3816183 polymorphisms are susceptible to hypospadias in Chinese Northern Han. Methods: We enrolled 113 patients with hypospadias and 182 healthy controls in the case-control study. Genotyping of single nucleotide polymorphisms (SNPs) was performed using High Resolution Melting (HRM). 113 hypospadias cases were further divided into anterior, middle and posterior subgroups for analysis. In addition, we performed a meta-analysis to evaluate the relationship in multiple populations. Results: The risk allele [C] of IRX6 rs6499755 was significantly associated with susceptibility to general hypospadias (OR = 1.547, p=0.01), anterior hypospadias (OR = 3.579, p=0.003) and posterior hypospadias (OR = 1.737, p=0.005). Besides, CC genotype carriers showed an increased risk of hypospadias compared with CT + TT carriers (OR = 1.832, p=0.026). The risk allele [T] of HAAO rs3816183 was associated with susceptibility to anterior/middle hypospadias (OR = 1.775, p=0.046). GMDR analysis revealed a significant interaction between IRX6 rs6499755 and HAAO rs3816183 in the risk of hypospadias (cross-validation consistency = 10/10, testing balanced accuracy = 0.6065, p=0.0010). The results of meta-analysis (including 3789 cases and 9241 controls) indicated that IRX6 rs6499755 and HAAO rs3816183 were significantly associated with hypospadias (both p < 0.00001). Conclusions: IRX6 rs6499755 and HAAO rs3816183 polymorphisms were associated with hypospadias in Chinese Northern Han, and there is a potential interaction between IRX6 rs6499755 and HAAO rs3816183 affecting the risk of hypospadias. The meta-analysis supported the hypothesis that IRX6 rs6499755 and HAAO rs3816183 were the susceptibility loci for hypospadias. Further research is needed to clarify their pathogenic mechanisms.

Background: This study aims to investigate the mutation spectrum of β-thalassemia in Fujian Province, China, and to comprehensively analyze the correlation between age, gender, genotype, and hematological parameters in carriers of β-thalassemia. Methods: Genotypes of 10,350 subjects suspected of having thalassemia were analyzed using reverse dot blotting (RDB) or β-globin gene sequencing. Their hematological indices were analyzed by genotype, gender, and age. Results: Among the subjects, 1214 (11.73%) were identified as β-thalassemia carriers. The prevalent genotypes included IVS-II-654 (C > T)/N (37.56%), CD 41-42 (-TTCT)/N (30.72%), CD 17 (A > T)/N (9.64%), -28 (A > G)/N (7.00%), CD 27-28 (+C)/N (3.21%), and CD 26 (GAG > AAG)/N (3.05%). Two rare mutations, Cap+22 (G > A) and IVS-II-806 (G > C), were detected, with the latter being part of a double heterozygous condition with hemoglobin (Hb) New York, compound -α4.2/αα, and Hb Q Thailand, marking the first report in Chinese individuals. Hematological analysis revealed that the CD 26 group exhibited higher levels of Hb, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) compared to the β⁰ and β⁺ groups (p < 0.05). Within the β⁺ group, individuals with -28 (A > G)/N showed significantly higher Hb, MCV, and MCH levels compared to those with IVS-II-654 (C > T)/N. Adult males had higher Hb levels than adult females, and adult patients generally had higher MCV and MCH levels than minors (p < 0.05). Conclusion: This study represents the first comprehensive molecular epidemiological investigation and hematological analysis of β-thalassemia in Fujian Province, providing support for the optimization of prevention and control strategies for thalassemia.

Background: This study aims to investigate the causal relationships between 12 micronutrients and common chronic respiratory diseases, revealing whether these nutrients play a causative role in either preventing or exacerbating these conditions. Methods: We employed a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationships between micronutrients and chronic respiratory diseases. Data were sourced from the IEU GWAS database, with micronutrients serving as exposure variables and chronic respiratory diseases as outcome variables for causal assessment. This was followed by reverse MR analysis, where the steps were reversed. Analytical methods included inverse-variance weighting (IVW), MR-Egger regression, and the weighted median method to correct for potential pleiotropy and reverse causality. Cochran's Q test and the MR-PRESSO method were used for pleiotropy tests to ensure robustness and reliability of the results. Results: The MR analysis revealed that the genetically predicted calcium is a protective factor for asthma (OR = 0.99, 95% CI 0.984-0.995, p < 0.01), vitamin B12 is a risk factor for asthma (OR = 1.015, 95% CI 1.005-1.024, p < 0.01), and vitamin E is a protective factor for idiopathic pulmonary fibrosis (IPF) (OR = 0.952, 95% CI 0.916-0.989, p=0.012). In the reverse MR analysis, asthma showed a potential causal relationship with calcium levels (OR = 0.829, 95% CI 0.704-0.976, p=0.025), while pneumoconiosis showed a potential risk causal relationship with calcium levels (OR = 1.003, 95% CI 1.002-1.004, p < 0.010). Additionally, pneumoconiosis was found to have a potential protective causal relationship with vitamin E levels (OR = 0.999, 95% CI 0.999-1.000, p=0.034), and sarcoidosis was found to have a potential protective causal relationship with vitamin B12 levels (OR = 0.989, 95% CI 0.979-1.000, p=0.044). Conclusion: This study shows significant causal associations among calcium, vitamin B12, and vitamin E with chronic respiratory diseases. There is a bidirectional protective causal relationship between calcium and asthma, suggesting that increasing calcium intake may reduce the risk of asthma. However, the causal relationships among other vitamins, minerals, and chronic respiratory diseases remain inconclusive, necessitating further research to validate these findings' robustness and generalizability.

Type 2 diabetes mellitus (T2DM) is a global health concern, particularly prevalent in low to middle-income countries like Bangladesh. This case-control study aims to explore the correlation between the ADIPOQ rs1501299 polymorphism and susceptibility to T2DM among the population of Noakhali region of Bangladesh. The study, involving 152 T2DM patients and 118 healthy controls, explores the genetic underpinnings of T2DM, considering the rising prevalence in Bangladesh. The ADIPOQ gene, implicated in diabetes development, is examined for the rs1501299 polymorphism, known for its associations with insulin resistance and T2DM in various populations. Genotyping, conducted through PCR and RFLP analysis, reveals significant deviations from Hardy-Weinberg equilibrium for the TT genotype, suggesting potential demographic influences. Clinical and biochemical characteristics, including blood pressure and lipid levels, highlight the complex interplay between genetics, metabolic outcomes and cardiovascular health in T2DM patients. This study identifies a significant association between the ADIPOQ rs1501299 T allele and increased T2DM risk, emphasizing the need for personalized risk assessment. However, ADIPOQ rs1501299 did not show any substantial association with CVD in the studied population. Despite limitations in sample size and regional focus, this study provides valuable insights into the genetic landscape of T2DM in the Noakhali population, paving the way for future research and personalized therapeutic interventions in addressing the global T2DM epidemic.

Objectives: Cryptorchidism is a notorious innate malformation in children that always leads to oligospermatism or azoospermatism. Moreover, there is a relationship between oxidative stress and spermatogenesis dysfunction caused by cryptorchidism. Ferroptosis is associated with iron metabolism and oxidative stress as a novel form of cell death regulation, which is involved in the pathogenesis of many diseases. Hence, ferroptosis may play an important role in spermatogenesis dysfunction in case of cryptorchidism. Therefore, the purpose of this study was to identify the key ferroptosis-related genes that influence spermatogenesis in patients with cryptorchidism and provided new strategies for the prevention and treatment of spermatogenesis dysfunction in cryptorchidism patients in clinical practice. Methods: Gene expression information was downloaded from the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were selected using the limma R package. Next, one crucial module, Maroon, was identified via Weighted Gene Coexpression Network Analysis (WGCNA). Ferroptosis-related genes were downloaded from FerrDb v2 database. GO and KEGG analyses were subsequently conducted. Moreover, these differentially expressed ferroptosis-related genes (DE-FRGs) were intersected with the DEGs of AdPlus/AdMinus. Two key genes most closely associated with spermatogenesis dysfunction in cases of cryptorchidism were subsequently identified. Furthermore, immunohistochemistry (IHC) and Receiver Operating Characteristic (ROC) analyses were conducted to validate our conclusions. Finally, miRWalk3.0 and TargetScan were used to predict the pivotal target microRNAs. Results: One critical module and two hub genes that are strongly related to the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism were identified. Gene Set Enrichment Analysis, ROC and IHC analyses were conducted and the results revealed that BRDT and PARP11 might play critical roles in spermatogenesis dysfunction in patients with cryptorchidism. Conclusion: Our study identified two ferroptosis-related genes, BRDT and PARP11 might play a role in the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism, which provided a novel perspective for the prevention and treatment of spermatogenesis dysfunction in patients with cryptorchidism in clinical practice.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common and highly malignant subtype of renal cancer, characterized by significant lipid deposition. Research has indicated that its growth and metastasis are closely associated with fatty acid metabolism. Methods: In this study, we integrated TCGA transcriptome data, CPTAC proteomics data, and the single-cell dataset GSE152938 to identify differentially expressed genes related to fatty acid metabolism in ccRCC. Using the LASSO algorithm, we constructed a prognostic model based on these genes. Western blot and PCR analyses confirmed the expression levels of the ECI2 in ccRCC, while lentiviral transduction was used to investigate the effects of ECI2 expression on tumor biological behaviors. Results: Our findings demonstrated that ECI2 expression is downregulated in ccRCC, and lower ECI2 levels correlate with better patient prognosis. Functional assays showed that overexpression of ECI2 significantly inhibited the proliferation and migration of ccRCC cells and increased their sensitivity to the chemotherapeutic drug oxaliplatin. Conclusion: This study highlights the potential tumor-suppressive role of ECI2 in ccRCC and suggests its viability as a diagnostic and therapeutic target.

Backgrounds: Serine hydroxy methyltransferase 2 (SHMT2) exerts an essential function in the cellular serine/glycine biosynthesis and one-carbon metabolism. Accumulative evidence revealed that SHMT2 was involved in cancer initiation and development in several types of carcinomas such as glioma, intrahepatic cholangiocarcinoma and colorectal cancer. However, expression and role of SHMT2 in lung adenocarcinoma (LUAD) had not been fully investigated. Methods: Transcriptional information of SHMT2 was retrieved from TCGA database. mRNA and protein expression of SHMT2 were analyzed in LUAD tissues alongside adjacent normal lung tissues using quantitative RT-PCR and immunohistochemical staining. The prognostic significance of SHMT2 in LUAD was assessed through both univariate and multivariate statistical analyses. Results: SHMT2 was higher in LUAD tissues than that in adjacent lung tissues on transcriptional level, mRNA level, and protein level. Elevated SHMT2 protein levels were associated with increased tumor size, positive lymph node metastasis, and more advanced TNM stages. LUAD patients with high SHMT2 level had worse prognosis. Conclusions: Our research indicated that elevated SHMT2 expression is strongly linked to adverse clinical characteristics and poor prognosis in LUAD patients. Consequently, SHMT2 may represent a novel prognosis marker and a promising therapeutic target regarding the treatment of LUAD.

Introduction: The relationship between autoimmune diseases and cancer risk has been increasingly studied. Colorectal cancer, a common malignancy with high morbidity and mortality, has been closely linked to inflammatory bowel disease (IBD) in previous research. However, the association and pathogenesis between primary sclerosing cholangitis (PSC) in autoimmune diseases and colorectal cancer remain incompletely understood. Our study directly investigated the relationship between PSC and colorectal cancer, excluding the influence of IBD, and provided new insights into this association. Methods: Mendelian randomization (MR) analysis was first used to investigate the potential causal relationship between PSC and colorectal cancer. Sensitivity analyses were performed to verify the reliability of the MR results. Transcriptomic data were then analyzed based on the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, combined with clinical prognostic data for the final identification of core differential genes. Results: MR analysis demonstrated that genetic susceptibility to PSC was associated with an increased risk of colorectal cancer in a European population cohort (ratio: 1.038, 95% confidence interval: 1.016-1.060, and p < 0.001). Furthermore, sensitivity analyses confirmed the robustness of the MR results. Univariate and multivariate Cox analyses identified five core genes: NEDD4L, PPP1R1A, NRG1, KCNJ16, and NECAB2. Patients grouped according to high or low expression of NRG1 showed significant differences in their prognosis (p < 0.001). Conclusion: Our MR study provides evidence that genetic susceptibility to PSC is significantly associated with an increased risk of colorectal cancer in European populations. Analysis of transcriptomic data suggests that NRG1 can be used as a novel biomarker to predict patient prognosis when colorectal cancer and PSC coexist.

Purpose: The transcriptional regulatory factors binding to the polymorphic site C-1888T in the promoter region of the palate, lung, and nasal epithelium clone (PLUNC) gene were identified to investigate whether the C-1888T polymorphic site affects the transcriptional regulation and function of PLUNC gene. Materials and Methods: Three genotypes of C-1888T polymorphic locus were screened from established nasopharyngeal carcinoma (NPC) cells, and the mRNA expression levels of PLUNC gene in different genotypes were detected. The respective transcription factors that were more likely to bind with A or G in SNP were predicted by biological information and preliminarily verified in vitro by gel electrophoresis migration rate analysis. Ulteriorly, the NPC cell lines were analyzed through chromatin immunoprecipitation combined with PCR amplification to confirm that the transcription factors could bind to the PLUNC gene promoter. Results: The cell lines 5-8F, 6-10B, CNE1, and CNE2 were heterozygous CT type, SUNE1 was homozygous CC type, and C666-1 was homozygous TT type. The expression of PLUNC gene was significantly different among all cell lines (F = 33.844, p < 0.001), and the gene expression level of CC type was significantly lower than TT type (p < 0.001). Gel electrophoresis mobility analysis confirmed that the transcription factors XFD3 and EVI1 could bind to the PLUNC gene promoter when the SNP was A and G, respectively. PCR amplification combined with chromatin immunoprecipitation showed that EVI1 could bind to the DNA fragment of the promoter region of PLUNC gene in SUNE1 NPC cells. Conclusion: The transcription factors XFD3 and EVI1 may be involved in the transcriptional regulation of PLUNC gene, and EVI1 can bind to the promoter region of PLUNC gene in SUNE1 NPC cells, thus associated with the susceptibility/risk of NPC.