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European Journal of Medical Research Jun 2024Observational studies have found a link between two autoimmune diseases, namely, primary sclerosing cholangitis (PSC) and systemic lupus erythematosus (SLE). However,...
BACKGROUND
Observational studies have found a link between two autoimmune diseases, namely, primary sclerosing cholangitis (PSC) and systemic lupus erythematosus (SLE). However, the relationship remains unclear.
METHODS
Bidirectional Mendelian randomization (MR) analysis and statistical methods, including inverse variance weighting, weighted median, and MR-Egger tests, were performed using data from genome-wide association studies to detect a causal relationship between PSC and SLE. Sensitivity analyses were subsequently performed to assess the robustness of the results. Univariate MR methods were also investigated.
RESULTS
Results of MR analysis suggested that PSC was associated with an increased risk for SLE (odds ratio: 1.33, 95% confidence interval: 1.10-1.61, P=0.0039) However, SLE had no significant causal relationship with PSC.
CONCLUSION
Results of MR analysis revealed that patients with PSC were at an increased risk for SLE, which provides new insights into the relationship between these two autoimmune diseases.
Topics: Lupus Erythematosus, Systemic; Humans; Cholangitis, Sclerosing; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Risk Factors
PubMed: 38943194
DOI: 10.1186/s40001-024-01941-1 -
BMC Immunology Jun 2024Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by...
BACKGROUND
Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP).
RESULTS
Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02).
CONCLUSIONS
These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.
Topics: Humans; COVID-19; Receptors, KIR; Iran; Male; Female; Genetic Predisposition to Disease; SARS-CoV-2; Middle Aged; Adult; Severity of Illness Index; Haplotypes; Genotype; Gene Frequency; Killer Cells, Natural; Aged
PubMed: 38943065
DOI: 10.1186/s12865-024-00631-1 -
BMC Immunology Jun 2024Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence regarding the causal role of IMID and periodontal disease is still lacking. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to uncover the potential genetic causal effects between IMID and periodontal disease.
METHODS
Bidirectional two-sample MR analysis was employed. Data for ten IMIDs were sourced from genome-wide association studies (GWAS) conducted by the FinnGen Consortium (range from 1023 to 36321 cases) and UK Biobank (UKB) (range from 150 to 17574 cases). Furthermore, GWAS data for periodontal disease were obtained from the FinnGen Consortium (87497 cases), UKB (458 cases), and Gene Lifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 periodontitis cases). Subsequently, the causal relationships were analyzed by random effects inverse variance weighting, weighted median, and MR-Egger. Sensitivity analyses were performed using the Cochrane Q test, funnel plot, and Mr-Egger intercept test to ensure robustness. Eventually, replication analysis and meta-analysis across different databases were carried out.
RESULTS
Systemic lupus erythematosus (SLE) [IVW: OR = 1.079 (95% CI: 1.032-1.128) and P < 0.001], Sjogren syndrome [IVW: OR = 1.082 (95% CI: 1.012-1.157) and P = 0.022] and hypothyroidism [IVW: OR = 1.52 (95% CI: 1.13-2.04) and P = 0.005] may increase the risk of periodontal disease. In addition, periodontal disease may reduce the risk of SLE [IVW: OR = 0.8079 (95% CI: 0.6764-0.9650) and P = 0.019] and hyperthyroidism [IVW: OR = 5.59*10 (95% CI: 1.43*10-2.18*10) and P = 0.014]. Meta-analysis indicated a causal correlation between SLE and an increased risk of periodontal disease: [OR = 1.08 (95% CI: 1.03-1.13), P = 0.0009]. No significant evidence suggests bilateral causal relationships between other IMIDs and periodontal disease. No significant estimation of heterogeneity or pleiotropy is detected.
CONCLUSIONS
Our study has confirmed a genetic causal relationship between IMIDs and periodontal disease, thereby unveiling novel potential mechanisms underlying IMIDs and periodontal disease. This discovery is promising in fostering interdisciplinary collaboration between clinicians and stomatologists to facilitate appropriate and precise screening, prevention, and early treatment of IMIDs and periodontal disease.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Periodontal Diseases; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Inflammation; Lupus Erythematosus, Systemic
PubMed: 38943064
DOI: 10.1186/s12865-024-00634-y -
BMC Cancer Jun 2024Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating...
BACKGROUND
Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored.
METHODS
The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk.
RESULTS
MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers.
CONCLUSIONS
We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.
Topics: Humans; Lung Neoplasms; Male; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Middle Aged; Transcription Factors; Asian People; DNA-Binding Proteins; Transcription Factor MTF-1; Case-Control Studies; China; Aged; Genotype; Risk Factors; East Asian People
PubMed: 38943058
DOI: 10.1186/s12885-024-12516-y -
Mycoses Jul 2024Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with...
BACKGROUND
Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent.
OBJECTIVES
The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC).
METHODS
We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method.
RESULTS
Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L.
CONCLUSION
Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.
Topics: Antifungal Agents; Humans; Microsporum; Disease Outbreaks; Microbial Sensitivity Tests; Drug Resistance, Fungal; Male; Female; Denmark; Adult; Child; Terbinafine; Middle Aged; Tinea Capitis; Griseofulvin; Child, Preschool; Adolescent; Young Adult; Tinea; Itraconazole; Aged; Fluconazole
PubMed: 38943042
DOI: 10.1111/myc.13760 -
Scientific Reports Jun 2024Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading...
Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading cause of disability. Here, We used a two-sample Mendelian randomization approach using pooled statistics from genome-wide association studies of ISSHL (1491 cases, 196,592 controls) and depression (23,424 cases, 192,220 controls) in European populations. This study investigated the bidirectional relationship between single nucleotide polymorphisms associated with depression and ISSHL using inverse variance weighting.Additional sensitivity analyses, such as Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, were performed to assess the reliability of the findings. Significant causal association between genetic susceptibility to ISSHL and depression in a random-effects IVW approach (OR = 1.037, 95% CI = 1.004-1.072, P = 0.030). In contrast, genetic depression was not risk factors for ISSHL (OR = 1.134, 95% CI = 0.871-1.475, P = 0.350). After validation by different MR methods and the sensitivity analysis, all of the above results are consistent. The evidence we have gathered suggests a causal relationship between ISSHL and depression. The presence of the former induces or further exacerbates the latter, whereas a similar situation does not exist when the latter is an influencing factor.
Topics: Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Hearing Loss, Sensorineural; Genetic Predisposition to Disease; Genome-Wide Association Study; Depression; Hearing Loss, Sudden; Risk Factors
PubMed: 38942925
DOI: 10.1038/s41598-024-65966-6 -
Scientific Reports Jun 2024While there are currently over 40 replicated genes with mapped risk alleles for Late Onset Alzheimer's disease (LOAD), the Apolipoprotein E locus E4 haplotype is still...
While there are currently over 40 replicated genes with mapped risk alleles for Late Onset Alzheimer's disease (LOAD), the Apolipoprotein E locus E4 haplotype is still the biggest driver of risk, with odds ratios for neuropathologically confirmed E44 carriers exceeding 30 (95% confidence interval 16.59-58.75). We sought to address whether the APOE E4 haplotype modifies expression globally through networks of expression to increase LOAD risk. We have used the Human Brainome data to build expression networks comparing APOE E4 carriers to non-carriers using scalable mixed-datatypes Bayesian network (BN) modeling. We have found that VGF had the greatest explanatory weight. High expression of VGF is a protective signal, even on the background of APOE E4 alleles. LOAD risk signals, considering an APOE background, include high levels of SPECC1L, HLA-DRA and RANBP3L. Our findings nominate several new transcripts, taking a combined approach to network building including known LOAD risk loci.
Topics: Humans; Alzheimer Disease; Genetic Predisposition to Disease; Apolipoprotein E4; HLA-DR alpha-Chains; Female; Male; Aged; Adaptor Proteins, Signal Transducing; Alleles; Haplotypes; Bayes Theorem; Risk Factors; Nuclear Proteins; Aged, 80 and over
PubMed: 38942763
DOI: 10.1038/s41598-024-65010-7 -
Neuroimaging Clinics of North America Aug 2024Concepts of multiple sclerosis (MS) biology continue to evolve, with observations such as "progression independent of disease activity" challenging traditional... (Review)
Review
Concepts of multiple sclerosis (MS) biology continue to evolve, with observations such as "progression independent of disease activity" challenging traditional phenotypic categorization. Iron-sensitive, susceptibility-based imaging techniques are emerging as highly translatable MR imaging sequences that allow for visualization of at least 2 clinically useful biomarkers: the central vein sign and the paramagnetic rim lesion (PRL). Both biomarkers demonstrate high specificity in the discrimination of MS from other mimics and can be seen at 1.5 T and 3 T field strengths. Additionally, PRLs represent a subset of chronic active lesions engaged in "smoldering" compartmentalized inflammation behind an intact blood-brain barrier.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Brain; Biomarkers; Inflammation; Neuroimaging; Cerebral Veins
PubMed: 38942521
DOI: 10.1016/j.nic.2024.03.004 -
Developmental Cell Jun 2024Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of...
Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. FGFR1OP insufficiency hindered epithelial resilience during colitis. FGFR1OP was crucial for preserving non-muscle myosin II activity, ensuring the integrity of the actomyosin cytoskeleton and crypt cell adhesion. This role of FGFR1OP suggests that its deficiency in genetically predisposed individuals may reduce epithelial renewal capacity, heightening susceptibility to inflammation and disease.
PubMed: 38942017
DOI: 10.1016/j.devcel.2024.06.001 -
International Immunopharmacology Jun 2024Rheumatoid arthritis (RA) is a chronic systemic disease characterized by inflammatory synovitis, and genetic factors play the greatest role in RA. This study aimed to...
OBJECTIVE
Rheumatoid arthritis (RA) is a chronic systemic disease characterized by inflammatory synovitis, and genetic factors play the greatest role in RA. This study aimed to investigate the relationship between Toll-like receptor 10(TLR10) gene polymorphisms and susceptibility to RA.
METHODS
A total of 271 patients with RA and an equal number of healthy controls were included, and the TLR10 rs2101521, rs10004195 and rs11725309 loci were genotyped by time-of-flight mass spectrometry.
RESULTS
Compared with healthy controls, Individuals carrying the rs2101521 G allele had an increased risk of developing RA (P = 0.01; odds ratio (OR) = 1.367; 95 % confidence interval (CI): 1.076-1.736). Individuals with the rs2101521 GG genotype had a greater risk of RA (P = 0.01; OR = 1.816; 95 % CI: 1.161-2.984). Stratified analysis demonstrated a greater prevalence of positive anti-cyclic citrullinated peptide (CCP)antibody in patients carrying the rs2101521 G allele (P = 0.03). Additionally, patients with the rs11725309 CT genotype had elevated levels of C-reactive protein (CRP)(P = 0.007).
CONCLUSION
In conclusion, TLR10 gene polymorphisms are associated with RA susceptibility.
PubMed: 38941669
DOI: 10.1016/j.intimp.2024.112565