International journal of molecular epidemiology and genetics最新文献

COVID-19 vaccination, both in healthy individuals and those with comorbid medical disorders, has proven highly effective in mitigating critical disease progression and mortality rates. Nevertheless, although rare, induction of autoantibodies and new-onset autoimmune conditions in apparently healthy individuals receiving COVID-19 vaccination have been documented. These autoimmune phenomena can be broadly classified into organ-specific autoimmune disorders (e.g., subacute thyroiditis (SAT)) and systemic autoimmune disorders, with many being generally transient (e.g., vaccine-induced thrombotic thrombocytopenia (VITT)) and others causing chronic disability (e.g., systemic vasculitis). Recent studies have highlighted significant associations between COVID-19 vaccine-associated autoimmunity and human leukocyte antigen (HLA) loci. For example, HLA class I alleles such as HLA-B*35 and HLA-C*04 have been associated with COVID-19 vaccine-induced SAT, while HLA class II alleles, including HLA-DRB1*11:04, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DPB1*17:01, have been linked to VITT. This review synthesizes the reported associations between classical HLA loci and COVID-19 vaccine-induced autoimmunity, providing insights into potential mechanisms and clinical implications.

Background: Cholesteatoma recurrence is relatively common and often requires repeat surgical interventions, imposing a significant burden on patients and healthcare systems. Although clinical factors such as age, disease aggressiveness, surgical technique, and surgeon experience influence recurrence risk, accurate prediction remains challenging. Genetic Risk Scores (GRS), which aggregate the effects of multiple genetic variants, offer a promising approach to individualized recurrence risk estimation.

Objective: To evaluate the contribution of specific genetic variants to cholesteatoma recurrence by constructing a GRS using data from the UK Biobank.

Methods: A systematic review of PubMed identified six genes previously associated with cholesteatoma recurrence: KGF (FGF7), KGF-R (FGFR2), MMP9, KRT1, KRT10, and MIF. Corresponding single nucleotide polymorphisms (SNPs) were analyzed using the UK Biobank, a large-scale biomedical database of approximately 500,000 participants. Individuals with recurrent cholesteatoma were identified using ICD-10 code H95.0. SNPs with minor allele frequency <5% or in linkage disequilibrium were excluded. A weighted GRS was calculated by summing the number of risk alleles for each SNP, multiplied by their β coefficients (log odds ratios).

Results: A total of 39 SNPs were included in the final GRS calculation. Among 502,164 UK Biobank participants, 55 individuals were identified with recurrent cholesteatoma. The mean GRS for these individuals was 3.86, compared to 3.72 in the general population, indicating a 15.6% relative increase in genetically determined recurrence risk (OR ≈ 1.156).

Conclusions: This study demonstrates a modest but measurable contribution of genetic variation to cholesteatoma recurrence. While the effect size is limited, future studies with larger cohorts and genome-wide data may improve predictive accuracy. Even at this stage, the GRS may help guide surgical decision-making and follow-up planning, moving toward more personalized management of cholesteatoma.

Objectives: Epstein-Barr virus (EBV) associated gastric cancer (EBVaGC) represents a distinct subtype of gastric carcinoma clinically characterized by low frequency of lymph node metastasis and better prognosis as compared to the EBV-negative gastric cancer (EBVnGC). Differential expression analysis of the transcriptome from tumor tissues revealed frequent involvement of immune genes which emphasizes the exclusive significance of immune response in EBVaGC patients. Considering the reported over-expression of toll-like receptor (TLR) genes in EBV infection and giving the crucial roles of TLRs in the innate immune system, we assumed that the entire TLR signaling pathway could have been differentially regulated in EBVaGC.

Methods: We tested our hypothesis by performing a differential expression analysis of the whole TLR signaling pathway using gene set enrichment test.

Results: A self-matched test detected a significant upregulation of the TLR signaling pathway in tumor as compared with non-tumor gastric tissues of EBVaGCs (P = 4×10^-3) but no significant differential regulation of the pathway in EBVnGCs. A comparison of tumor gastric tissue in EBVaGCs versus non-tumor gastric tissue in EBVnGCs showed an even more significant upregulation of the pathway with a high enrichment of overexpressed genes (P = 2.5×10^-4).

Conclusions: Briefly, this study revealed a distinct pattern of activation of the TLR signaling pathway in EBVaGCs which can be seen as a specific feature of molecular pathology in the disease. This feature characterizes the disease as a distinct subtype of gastric cancer in oncogenesis which can be linked to its clinical manifestation and prognosis to motivate improved treatment strategies for both EBVaGC and EBVnGC patients.

Objectives: Women are at a significantly higher risk of osteoporotic fractures, largely due to progressive bone demineralization and impaired bone microarchitecture. Low bone mineral density (BMD) is a common condition in women worldwide. Disrupted homocysteine (Hcy) metabolism has been linked to reduced BMD and increased risk of osteoporotic fractures. Hyperhomocysteinemia (Hhcy) affects osteoblast and osteoclast activity, interferes with collagen cross-linking in the extracellular matrix, and has a detrimental effect on bone health. This study aimed to establish the association between hematological and biochemical parameters and osteoporosis in adult females. Methods: We measured Hcy, creatinine, uric acid (UA), vitamin B12, and vitamin D levels. Significantly elevated Hcy (27.322 ± 0.816 vs 10.152 ± 0.381 µmol/L), creatinine (0.670 ± 0.012 vs 0.587 ± 0.011 mg/dL), and UA (5.118 ± 0.083 vs 2.786 ± 0.060 mg/dL) were found in osteoporotic females, while reduced concentrations of vitamin B12 (148.883 ± 2.192 vs 294.14 ± 6.505 pg/mL) and vitamin D (24.98 ± 0.621 vs 33.7 ± 0.652 ng/mL) were observed. Results: Hematological parameters were found differentially expressed in osteoporotic females. Elevated Hcy levels, combined with reduced vitamin B12 and vitamin D, were strongly associated with decreased BMD and a higher susceptibility to osteoporotic fractures. Women with increased Hcy levels also had lower T-scores compared to those without Hhcy. Conclusions: These findings suggest that Hcy plays a critical role in bone resorption and osteoporotic fractures. Regulating Hcy metabolism may serve as an effective therapeutic strategy for managing bone resorption and osteoporosis. We hypothesize that elevated Hcy levels are closely related to low BMD and an increased risk of osteoporosis.

Artemisinin Combination Therapies (ACT) stand as the most potent antimalarial treatments. In response to the emergence of ACT-resistant malaria parasites in Southeast Asia, the World Health Organization (WHO) has recommended continuous monitoring of the effectiveness of ACT and other antimalarials. To address this need, we collected dried blood spots from malaria patients during a 42-days drug efficacy trial evaluating the efficacy of Artesunate plus Amodiaquine (ASAQ), Artemether Plus Lumefantrine (AL) and Dihydroarthemisinine plus Piperaquine (DHAPQ) on simple P. falciparum malaria in 2017. Blood samples were collected on Day 0, prior to the patients' initial ACT dose, and on any days of recurrent parasitemia. Genetic markers such as Merozoite Surface Protein 1 (MSP1) and Merozoite Surface Protein 2 (MSP2) were genotyped to differentiate between recrudescence and re-infestation cases. Furthermore, PCR Single Specific Oligonucleotide Probes combined with-ELISA platform (PCR-SSOP-ELISA) and PCR-RFLP techniques were used to identify Pfcrt 72-76 mutant haplotype and Pfmdr1_86Y allele associated with chloroquine and amodiaquine resistance, respectively. Out of the 320 patients enrolled in the study, only 43 (13.43%) experienced relapses. Upon PCR correction, our analysis revealed that recrudescent infections affected 13 patients, with 8 in the ASAQ group, 5 in the AL group, and none in the DHAPQ group. Notably, no early treatment failures (within the first 3 days of treatment) were observed, and all recurrences occurred between Day 21 and Day 42. The prevalence of the Pfcrt wild-type haplotype CVMNK and Pfmdr N86 allele was 67.03% and 97.70%, respectively. In contrast, the mutant types CVIET and 86Y were found at 32.97% and 2.3%, respectively. The high prevalence of the CVMNK wild haplotype suggests that the parasites remain sensitive to chloroquine, while the low prevalence of the 86Y mutants indicates continued effectiveness of amodiaquine. Furthermore, the low prevalence of strains exhibiting the combination of CVIET and 86Y suggests that the use of multiple antimalarials is valuable for resistance control. Notably, none of the relapse cases carried the 86Y mutation or the combination of 86Y and CVIET.

University campus communities consist of dynamic and diverse human populations originated from different regions of the country or the world. Their national/global movement to and from campus may contribute to the spread and buildup of methicillin-resistant (MR) bacteria, including MR Staphylococci (MRS) on high-touch surfaces, sinks, and toilets. However, studies on MR bacteria contamination of surfaces, sinks, and toilets are scarce in workplaces outside of healthcare settings. Hence, little is known whether university communities contaminate campus bathrooms by MR bacteria. This study evaluated the abundance, identity, and phylogenetics of MR bacteria grown on CHROMagar MRSA media from bathrooms at workplaces. We collected 21 sink and 21 toilet swab samples from 10 buildings on campus and cultured them on CHROMagar MRSA media, extracted DNA from MR bacteria colonies, sequenced PCR products of 16S and dnaJ primers, determined the sequence identities by BLAST search, and constructed a phylogenetic tree. Of 42 samples, 57.1% (24/42) harbored MR bacteria. MR bacteria were more prevalent on the sink (61.9%) than in the toilet (52.2%) and in male bathrooms (54.2%) than in female bathrooms (41.7%). The colony count on the bathroom surfaces of 42 samples varied in that 42.9% (18/42), 33.3, 14.3, and 9.5% of samples harbored 0, 100, and > 1000 MR bacteria colonies, respectively. Of MR bacteria sequenced, BLAST search and phylogenetic analysis showed that Staphylococcus accounted for 60% of the MR bacteria and the rest were non-Staphylococci. Of Staphylococcus carrying MR (n = 15), 53.3% were S. hemolyticus followed by S. lugdunensis (26.7%), S. epidermidis (8%), and a newly discovered S. borealis in 2020 (4%). Of non-Staphylococci MR bacteria, 20% accounted for Sphingomonas koreensis. Campus bathrooms serve as a reservoir for diverse bacteria carrying MR, which pose a direct risk of infection and a potential source of horizontal gene transfer. To reduce the health risk posed by MR bacteria in high traffic areas such as bathrooms additional environmental monitoring and improved decontamination practices are needed.

Objective: In recent years, Acinetobacter baumannii has been appearing in hospitals with high drug resistance and strong vitality, which brings many difficulties to clinical treatment. In this study, 255 strains of A. baumannii were isolated from Youjiang Medical University for Nationalities Affiliated Hospital clinical samples and found to be highly resistant to carbapenems. The drug resistance, biofilm-forming ability, and carbapenase gene distribution of 145 carbapenem-resistant A. baumannii (CRAB) strains were analyzed statistically.

Methods: The clinically isolated strains were detected using Vitek mass spectrometry and Vitek2-compact for bacterial identification and susceptibility testing, respectively. The biofilms of clinical isolates were quantitatively detected by microplate crystal violet staining, and qualitatively observed by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). And the common carbapenemase genes were detected by polymerase chain reaction (PCR).

Results: The 255 clinical isolates from the Youjiang District of western Guangxi Province had a high resistance rate to carbapenems antibiotics. The main specimens were from the intensive care unit (49%), and the most important specimens were sputum specimens (80%). All 145 strains of CRAB produced different degrees of biofilm, and six carbapenenase genes were detected. We found that there were significant differences in biofilm formation between resistant and sensitive strains of tobramycin, levofloxacin, ciprofloxacin, tigecycline, and doxycycline (P<0.05). The distribution of bla_OXA-23 and bla_OXA51 genes was significantly different from CRAB biofilm formation (P<0.05). In addition, AmpC, bla_OXA-23, bla_OXA-51, and TEM genes were more distributed in antibiotic-resistant strains.

Conclusion: The clinical strains have a high resistance rate to carbapenems, and the CRAB with bla_OXA-51 and bla_OXA-23 genes has a high resistance to antibiotics and a strong biofilm.

Turner-type X-linked syndromic intellectual developmental disorder (MRXST) is a rare neurodevelopmental disorder. MRXST is caused by pathogenic variants in the HUWE1 gene on chromosome Xp11.22. The HUWE1 gene encodes a ubiquitin ligase, which has downstream effects on the n-MYC protein and DLL3 Notch ligand, ultimately affecting neuronal differentiation. In addition to intellectual disability and developmental delay, other clinical features such as absent or delayed speech, skeletal abnormalities, abnormalities in hands or feet, seizures, and hypotonia have been described in case reports. Facial dysmorphic features and eye manifestations have been reported in patients with MRXST, but have not been identified as distinctive to this condition. We report two cases of individuals affected by HUWE1-Related Intellectual Developmental Disorder and present a review of literature of male patients affected by this disorder. Based on the literature review and findings in our two patients, it is our observation that patients with MRXST present with distinctive features, which include broad nasal tip, root, or prominent nose (39%), blepharophimosis (27%), epicanthic folds (25%), ear abnormalities (25%), thin upper lip (23%), and deep set eyes (23%). Furthermore, we note that oculofacial abnormalities are seen more frequently in patients with missense variants than patients with duplications in the HUWE1 gene. The findings noted in this paper may help clinicians suspect a diagnosis of MRXST when presented with these distinctive ocular and facial features.

Objective: The aim of this study was to identify the potential risk factors and genetic variants associated with dental caries incidence using survival analysis.

Methods: The Center for Oral Health Research in Appalachia recruited and prospectively followed pregnant women and their children. A total of 909 children followed from birth for up to 7 years were included in this study. Annual intra-oral examinations were performed to assess dental caries experience including the approximate time to first caries incidence in the primary dentition. Cox proportional hazards models were used to assess the associations of time to first caries incidence with self-reported risk factors and 4.9 million genetic variants ascertained using a genome-wide genotyping array.

Results: A total of 196 of 909 children (21.56%) had their first primary tooth caries event during follow-up. Household income, home water source, and mother's educational attainment were significantly associated with time to first caries incidence in the stepwise Cox model. The heritability (i.e., proportion of variance explained by genetics) of time to first caries was 0.54. Though no specific genetic variants were associated at the genome-wide significance level (P < 5E-8), we identified 14 loci at the suggestive significance level (5E-8 < P < 1E-5), some of which were located within or near genes with plausible biological functions in dental caries.

Conclusion: Our findings indicate that household income, home water source, and mother's educational attainment are independent risk factors for dental caries incidence. We nominate several suggestive loci for further investigation.

Introduction: miR-132-3p acts in normal breast development and its downregulation has been documented in breast cancer. One of the targets of miR-132-3p is RB1 which is also inactivated in breast cancer. The interactions between RB1 and miR-132 have been reported in several pathological conditions. We aimed to investigate the correlation between expression levels of miR-132 and RB1 in ductal carcinoma of the breast.

Methods: The study was carried out on tissues obtained from female patients with primary breast cancer. Tumor samples were classified using clinical and pathological data. Following RNA extraction and cDNA synthesis, relative gene expressions in tumors were compared to non-cancerous adjacent tissues. The link between RB1 and miR-132 was assessed by the correlation coefficient test.

Results: Our findings revealed a significant decrease in miR-132 and RB1 expressions with a ratio of 0.165 and 0.365, respectively. Tumor grade showed an association with miRNA-132 levels. The expression of miR-132 in grade I tumors was almost equal to that of normal adjacent tissues, but was intensely decreased in grades II and III. The correlation analysis showed a small linear association between RB1 and miR-132 levels.

Conclusion: The reduction of miR-132 and RB1 expression confirmed the tumor-suppressive role of both genes in breast cancer. Considering that RB1 is one of the miR-132 targets, further studies are required to discover any miRNA-mediated upregulation role for miR-132. Our finding discovered a small linear association between miR-132 and RB1, which can be concluded towards their independent function in breast cancer pathogenesis.