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Asian Pacific Journal of Cancer... Jun 2024Inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are diseases that result from the combined effects of a predisposing genetic...
BACKGROUND
Inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are diseases that result from the combined effects of a predisposing genetic background and several environmental factors, including smoking. Some genes can influence these diseases through genetic inheritance, and their regulation is explained by gene polymorphism. However, Toll-like receptor (TLR) genes have been identified as susceptibility genes for CD and UC.
METHODS
A case-control study was performed on a Turkish population composed of 105 healthy controls and 79 CD, 77 UC patients genotyped by Allele-specific PCR and PCR-RFLP for TLR9 (T-1486C) and TLR 2 (-196 to -174del) gene. Genotype and allele frequencies of TLR9 (T-1486C) and TLR 2 (-196 to -174del) gene polymorphisms compared to allele frequencies in CD and UC patients.
RESULTS
No statistically significant findings were found between the CD, UC patients, and the control group in terms of both genotype distributions and allele frequencies for TLR 9 (T-1486C; rs187084) and TLR 2 (-196 to -174del; rs111200466) gene polymorphisms in a Turkish population (P > 0.05).
CONCLUSION
No association was found between the TLR2 (rs111200466) and TLR 9 (rs187084) gene polymorphisms among IBD patients and the control groups in the Turkish population.
Topics: Humans; Toll-Like Receptor 2; Case-Control Studies; Male; Female; Genetic Predisposition to Disease; Toll-Like Receptor 9; Adult; Crohn Disease; Genotype; Inflammatory Bowel Diseases; Colitis, Ulcerative; Turkey; Gene Frequency; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Follow-Up Studies; Young Adult
PubMed: 38918662
DOI: 10.31557/APJCP.2024.25.6.2003 -
Asian Pacific Journal of Cancer... Jun 2024The BRCA1/2 mutation status testing is the global standard of care for breast cancer patients with a family history of cancer. BRCA1/2 mutations are known to be...
OBJECTIVE
The BRCA1/2 mutation status testing is the global standard of care for breast cancer patients with a family history of cancer. BRCA1/2 mutations are known to be ethno-specific. For some ethnic groups of the Northern Asia (Buryats, Yakuts, Altaians, Tuvans, Khakasses, etc.) the founder mutations in the BRCA1/2 genes have not been revealed. This systematic review was conducted to assess the prevalence of BRCA1/2 mutation in breast cancer patients inhabiting Eastern Europe and Northern Asia (or Siberia).
METHODS
A total of 23,561 studies published between 2014 and 2024 were analyzed, of which 55 were included in the review. The literature search was conducted using RusMed, Cyberleninka, Google Scholar, eLibrary, NCBI databases (n=5) and conference papers.
RESULTS
The founder mutations (c.5266dupC and/or c.181T>G) of BRCA1 gene that were frequently observed in the Slav peoples were also identified in Chechens, Armenians, Bashkirs, Ukrainians, Mordovians, Mari, Kabardians, Tatars, Uzbeks, Kyrgyz, Ossetians, Khanty indigenous peoples and Adygs. For Chechens, Kabardians, Ingush, Buryats, Khakasses, Sakha, Tuvans and Armenians, rare pathogenic variants of the BRCA1/2, ATM, СНЕК2, BRIP1, NBN, PTEN, TP53, PMS1, XPA, LGR4, BRWD1 and PALB2 genes were found. No data are available about the frequency of pathogenic BRCA1/2 mutations for ethnic groups, such as the Udmurts, Komi, Tajiks, Tabasarans, and Nogais indigenous people.
CONCLUSION
This is the first systematic review that provides the spectrum of BRCA mutations in ethnic groups of breast cancer patients inhabiting Eastern Europe and Northern Asia. It has been shown that the mutations are ethnospecific (varied widely within groups) and not all groups are equally well studied. Further studies on the ethnic specificity of BRCA gene mutations are required.
Topics: Humans; Breast Neoplasms; Female; BRCA1 Protein; Germ-Line Mutation; BRCA2 Protein; Genetic Predisposition to Disease; Prevalence; Asia; Prognosis
PubMed: 38918649
DOI: 10.31557/APJCP.2024.25.6.1891 -
PLoS Neglected Tropical Diseases Jun 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with susceptibility influenced by meteorological factors. However, there is limited...
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with susceptibility influenced by meteorological factors. However, there is limited understanding of the delayed and interactive impacts of meteorological factors on SFTS incidence.
METHODS
Daily incidence data of SFTS and corresponding meteorological factors for the Jiaodong Peninsula in northeast China were collected from January 1, 2014, to December 31, 2020. Random forest regression model, based on custom search, was performed to compare the importance of meteorological factors. Generalized additive model with quasi-Poisson regression was conducted to examine the nonlinear relationships and interactive effects using penalized spline methods. A distributed lag nonlinear model with quasi-Poisson regression was constructed to estimate exposure-lag effects of meteorological factors.
RESULTS
The most important meteorological factor was weekly mean lowest temperature. The relationship between meteorological factors and SFTS incidence revealed a nonlinear and intricate pattern. Interaction analyses showed that prolonged sunshine duration posed a climatic risk within a specific temperature range for SFTS incidence. The maximum relative risk (RR) observed under extremely low temperature (-4°C) was 1.33 at lag of 15 week, while under extremely high temperature (25°C), the minimum RR was 0.65 at lag of 13 week. The RRs associated with both extremely high and low sunshine duration escalated with an increase in lag weeks.
CONCLUSIONS
This study underscores that meteorological factors exert nonlinear, delayed, and interactive effects on SFTS incidence. These findings highlight the importance of understanding the dependency of SFTS incidence on meteorological factors in particular climates.
PubMed: 38917232
DOI: 10.1371/journal.pntd.0012266 -
PloS One 2024Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive... (Observational Study)
Observational Study
Influence of frailty on cardiovascular events and mortality in patients with Chronic Obstructive Pulmonary Disease (COPD): Study protocol for a multicentre European observational study.
BACKGROUND
Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Recent studies on COPD have shown that patients living with frailty have an increased risk of mortality. The presence of cardiovascular diseases or conditions are common in COPD and may increase the risk of death.
METHODS
This protocol describes a European prospective cohort study of community-based people, in a stable condition with diagnosis of COPD (as defined by GOLD guidelines) across hospitals in Italy and UK. Frailty prevalence will be assessed using the Clinical Frailty Scale. At 1- and 2-year follow up, primary outcome will be the impact of frailty on the number of cardiovascular events; secondary outcomes: the influence of frailty on cardiovascular mortality, all-cause mortality, and deaths due to COPD. For the primary outcome a zero-inflated Poisson regression will compare the number of cardiovascular events at 1 year. Secondary outcomes will be analysed using the time to mortality.
DISCUSSION
This multicentre study will assess the association between frailty and cardiovascular events and mortality in population with COPD. Data collection is prospective and includes routine clinical data. This research will have important implications for the management of patients with COPD to improve their quality of care, and potentially prognosis.
TRIAL REGISTRATION NUMBER
NCT05922202 (www.clinicaltrials.gov).
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Cardiovascular Diseases; Frailty; Prospective Studies; Aged; Male; Europe; Female; Risk Factors
PubMed: 38917212
DOI: 10.1371/journal.pone.0300945 -
PloS One 2024Hypertension is one of the most common and complicated disorders associated with genetic and environmental risk factors. The angiotensin-converting enzyme (ACE) is...
Hypertension is one of the most common and complicated disorders associated with genetic and environmental risk factors. The angiotensin-converting enzyme (ACE) is important in the renin-angiotensin-system pathway. The gene expression of ACE has been investigated as a possible hypertension marker. This study investigates the association between polymorphisms within the ACE1 and ACE2 genes and hypertension susceptibility in a Jordanian population. The study comprised a total of 200 hypertensive patients and 180 healthy controls. A polymerase chain reaction (PCR) was performed to genotype the candidate polymorphism (rs4646994) of the ACE1gene. The Luminex DNA array technique was used for genotyping SNPs (rs4359, rs4344, rs4341, rs4343, and rs2106809) of the ACE1 and ACE2 genes. Our findings suggest no association between SNPs and hypertension regarding allelic and genotypic frequencies. However, rs4359 was significantly associated with diet (pP = 0.049), know HTN (P = 0.042), and number of years DM (P = 0.003). rs4341 was associated with diet (P = 0.032), peripheral vascular disease (P = 0.005), and chronic kidney disease (p = 0.049). While rs4343 was associated with diet (P = 0.031), diabetes mellitus (P = 0.032), and other medication (P = 0.025). Furthermore, the haplotypes of four SNPs of the ACE1 gene showed no significant association with HTN patients and healthy controls. Our findings indicate no association between the polymorphisms in the ACE gene and the risk of hypertension development in the Jordanian adult population.
Topics: Humans; Hypertension; Jordan; Peptidyl-Dipeptidase A; Male; Female; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Middle Aged; Adult; Case-Control Studies; Angiotensin-Converting Enzyme 2; Gene Frequency; Genotype; Aged
PubMed: 38917192
DOI: 10.1371/journal.pone.0304271 -
The Journal of Clinical Investigation Jun 2024Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving...
Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving graft-versus-leukemia (GVL) effects. We observed differential expression of TIM-3 ligands when hematopoietic stem cells overexpressed certain oncogenic-driver mutations. Anti-TIM-3 Ab-treatment improved survival of mice bearing leukemia with oncogene-induced TIM-3 ligand expression. Conversely, leukemia cells with low ligand expression were anti-TIM-3 treatment-resistant. In vitro, TIM-3 blockade or genetic deletion in CD8+ T cells (Tc) enhanced Tc activation, proliferation and IFN-γ production while enhancing GVL effects, preventing Tc exhaustion and improving Tc cytotoxicity and glycolysis in vivo. Conversely, TIM-3 deletion in myeloid cells did not affect allogeneic Tc proliferation and activation in vitro, suggesting that anti-TIM-3-treatment-mediated GVL effects are Tc-induced. In contrast to anti-PD-1 and anti-CTLA-4-treatment, anti-TIM-3-treatment did not enhance acute graft-versus-host-disease (aGVHD). TIM-3 and its ligands were frequently expressed in acute myeloid leukemia (AML) cells of patients with post-allo-HCT relapse. We deciphered the connection between oncogenic mutations found in AML and TIM-3 ligands expression and identify anti-TIM-3-treatment as a strategy to enhance GVL effects via metabolic and transcriptional Tc-reprogramming, without exacerbation of aGVHD. Our findings support clinical testing of anti-TIM-3 Abs in patients with AML relapse post-allo-HCT.
PubMed: 38916965
DOI: 10.1172/JCI177460 -
International Journal of... Apr 2024The current meta-analysis aims to explore the potential correlation between natural resistance-associated macrophage protein 1 (NRAMP1) (3'-Untranslated region [3'-UTR])... (Meta-Analysis)
Meta-Analysis Review
A Systemic Review and Meta-analysis on Natural Resistance-associated Macrophage Protein 1 (3'-Untranslated Region) and Nucleotide-binding Oligomerization Domain-2 (rs8057341) Polymorphisms and Leprosy Susceptibility in Asian and Caucasian Populations.
The current meta-analysis aims to explore the potential correlation between natural resistance-associated macrophage protein 1 (NRAMP1) (3'-Untranslated region [3'-UTR]) and nucleotide-binding oligomerization domain-2 (NOD2 [rs8057341]) gene polymorphisms and their association with leprosy susceptibility in both Asian and Caucasian populations. Datas were retrieved from case control studies with NOD 2 and NRAMP 1 gene polymorphism associated with leprosy disease. Leprosy emerges as a particularly distinctive ailment among women on a global scale. The NRAMP1 (3'-UTR) and NOD2 (rs8057341) genetic variations play a crucial role in the progression of leprosy. A systematic review of relevant case-control studies was conducted across several databases, including ScienceDirect, PubMed, Google Scholar, and Embase. Utilizing MetaGenyo and Review Manager 5.4 Version, statistical analyses were carried out. Nine case-control studies totaling 3281 controls and 3062 leprosy patients are included in the research, with the objective of examining the potential association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk. The review methodology was registered in PROSPERO (ID520883). The findings reveal a robust association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk across various genetic models. Although the funnel plot analysis did not identify publication bias, bolstering these findings and elucidating potential gene-gene and gene-environment interactions require further comprehensive epidemiological research. This study identified a strong correlation between polymorphisms in the NOD2 (rs8057341) genes and susceptibility to leprosy across two genetic models. Further comprehensive epidemiological investigations are warranted to validate these findings and explore potential interactions between these genes and environmental factors.
Topics: Humans; Leprosy; Genetic Predisposition to Disease; Asian People; White People; Cation Transport Proteins; Nod2 Signaling Adaptor Protein; 3' Untranslated Regions; Polymorphism, Single Nucleotide; Case-Control Studies; Female; Polymorphism, Genetic; Male
PubMed: 38916380
DOI: 10.4103/ijmy.ijmy_43_24 -
Reumatismo Jun 2024To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA).
OBJECTIVE
To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA).
METHODS
In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software.
RESULTS
An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism.
CONCLUSIONS
rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.
Topics: Humans; Arthritis, Rheumatoid; Polymorphism, Single Nucleotide; Male; Female; Case-Control Studies; Middle Aged; Cuba; Adult; Adaptor Proteins, Signal Transducing; Genotype; Genetic Predisposition to Disease; Aged
PubMed: 38916163
DOI: 10.4081/reumatismo.2024.1691 -
Frontiers in Endocrinology 2024Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis...
PURPOSE
Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.
MATERIAL AND METHOD
We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.
RESULT
Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.
CONCLUSION
This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Quantitative Trait Loci; Genetic Predisposition to Disease; Bayes Theorem; Diabetes Mellitus, Type 1; Genomics; Hypoglycemic Agents; Polymorphism, Single Nucleotide
PubMed: 38915894
DOI: 10.3389/fendo.2024.1366290 -
Frontiers in Endocrinology 2024This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
PURPOSE
This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
MATERIAL AND METHOD
A dual-sample Mendelian randomization (MR) analysis was conducted using the publicly available genome-wide association study (GWAS) data. The inverse variance weighted based on the random effects model (Re-IVW) method was used as the main statistical analysis. Complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were applied to detect or correct the impact of horizontal pleiotropy.
RESULT
Re-IVW showed a genetic predictive causal relationship of phimosis on glomerulonephritis (odds ratio [OR]: 1.37 [1.13-1.65], = 0.00149) and IgA glomerulonephritis (OR: 1.57 [1.18-2.09), = 0.00187). Suggestive evidence indicated that phimosis was associated with chronic nephritis syndrome (OR: 1.23 (1.00-1.51), p = 0.0481], acute nephritis syndrome (OR: 1.50 [1.13-2.01], = 0.0058), and impotence (OR: 1.39 [1.11-1.73], = 0.0035). Kidney and ureteral stone (OR: 1.14 [1.04-1.26], = 0.0069), urethral strictures (OR: 1.26 [1.07-1.48], = 0.0050), benign prostatic hyperplasia (OR: 1.07 [1.01-1.13], = 0.0242), and decreased testicular function (OR: 0.72 [0.56-0.94], = 0.0141) have genetically predictive causal relationships.
CONCLUSION
In summary, we employed a series of reliable analytical methods to investigate the association between phimosis and 26 urogenital diseases. We have reported several strong associations, but more research is needed to evaluate whether this discovery is replicated in other environments and to gain a better understanding of potential mechanisms.
Topics: Humans; Mendelian Randomization Analysis; Male; Genome-Wide Association Study; Phimosis; Female Urogenital Diseases; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38915890
DOI: 10.3389/fendo.2024.1308270