UNASSIGNED: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.
UNASSIGNED: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations.
UNASSIGNED: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis.
UNASSIGNED: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.

UNASSIGNED: In the present study, we evaluated whether DEFB1 gene polymorphisms are associated with the presence of coronary artery disease (CAD).
UNASSIGNED: Two rs11362 A/G, and rs1800972 C/G gene polymorphisms of DEFB1 gene were genotyped by 5\'exonuclease TaqMan assays in 219 patients with CAD and 522 control individuals.
UNASSIGNED: The distribution of rs1800972 C/G polymorphisms was similar in patients with CAD and healthy controls. Nonetheless, under the co-dominant, dominant, recessive, and additive models, the AA genotype of the rs11362 A/G polymorphism was associated with the risk of developing CAD (OR = 1.89 pCCo-Dom = 0.041, OR = 1.46, pCDom = 0.034, OR = 1.69, pCRes = 0.039, and OR = 1.37, pCAdd = 0.012, respectively). In addition, the linkage disequilibrium showed that the \'AG\' haplotype was associated with an increased risk of developing CAD (OR = 1.23, p = 0.042). According, with the Genotype-Tissue Expression (GTEx) consortium data, the rs11362 AA genotype is associated with a low mRNA expression of the β-defensin-1 in tissues, such as artery aorta, artery coronary, heart left ventricle, and heart atrial appendage (p < 0.001).
UNASSIGNED: This study demonstrates that rs11362 A/G polymorphism of the DEFB1 gene is involved in the risk of developing CAD, and with a low RNA expression of the β-defensin-1 in heart tissue.

Understanding the mechanisms underlying alcohol metabolism and its regulation, including the effect of polymorphisms in alcohol-metabolizing enzymes, is crucial for research on Fetal Alcohol Spectrum Disorders. The aim of this study was to identify specific single nucleotide polymorphisms in key alcohol-metabolizing enzymes in a cohort of 71 children, including children with fetal alcohol syndrome, children prenatally exposed to ethanol but without fetal alcohol spectrum disorder, and controls. We hypothesized that certain genetic variants related to alcohol metabolism may be fixed in these populations, giving them a particular alcohol metabolism profile. In addition, the difference in certain isoforms of these enzymes determines their affinity for alcohol, which also affects the metabolism of retinoic acid, which is key to the proper development of the central nervous system. Our results showed that children prenatally exposed to ethanol without fetal alcohol spectrum disorder traits had a higher frequency of the ADH1B*3 and ADH1C*1 alleles, which are associated with increased alcohol metabolism and therefore a protective factor against circulating alcohol in the fetus after maternal drinking, compared to FAS children who had an allele with a lower affinity for alcohol. This study also revealed the presence of an ADH4 variant in the FAS population that binds weakly to the teratogen, allowing increased circulation of the toxic agent and direct induction of developmental abnormalities in the fetus. However, both groups showed dysregulation in the expression of genes related to the retinoic acid pathway, such as retinoic acid receptor and retinoid X receptor, which are involved in the development, regeneration, and maintenance of the nervous system. These findings highlight the importance of understanding the interplay between alcohol metabolism, the retinoic acid pathway and genetic factors in the development of fetal alcohol syndrome.

Infection by the recent SARS-CoV-2 virus causes the COVID-19 disease with variable clinical manifestations ranging from asymptomatic or mild respiratory symptoms to severe respiratory distress and multiorgan failure. The renin-angiotensin system, responsible for maintaining homeostasis and governing several critical processes, has been considered the main system involved in the pathogenesis and progression of COVID-19. Here, we aimed to assess the possible association between variants in the RAS-related genes and COVID-19 susceptibility and severity in a sample of the Moroccan population. A total of 325 individuals were recruited in this study, with 102 outpatients, 105 hospitalized patients, and 118 healthy controls negative for SARS-CoV-2 infection, and subjected to NGS gene panel sequencing containing eleven RAS pathway genes. A total of 65 functional variants were identified, including 63 missenses, 1 splice, and 1 INDEL. Most of them were rare, with 47 (72%) found in a single individual. According to the common disease/common variant hypothesis, five common candidate variants with MAF > 10% were identified (ACE2 rs2285666, TMPRSS2 rs12329760, AGT rs699 genes, ACE rs4341, and ACE rs4343). Statistical analysis showed that the ACE rs4343 AA genotype was associated with a 2.5-fold increased risk of severe COVID-19 (p = 0.026), and the T genotype of the ACE2 rs2285666 variant showed a borderline association with susceptibility to SARS-CoV-2 in males (p = 0.097). In conclusion, our results showed that the RAS pathway genes are highly conserved among Moroccans, and most of the identified variants are rare. Among the common variants, the ACE rs4343 polymorphism would lead to a genetic predisposition for severe COVID-19.

UNASSIGNED: Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL-6 single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL-6 in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL-6 and the susceptibility to breast carcinoma among women in Bangladesh.
UNASSIGNED: The IL-6 rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra-primer ARMS-PCR method. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL-6 mRNA analysis, and genotype-based gene expression was retrieved from GTEx Portal.
UNASSIGNED: This study found a significant link between IL-6 rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AG vs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AG vs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AA vs. GG: OR = 2.91, p > 0.05) and the recessive model (AA vs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25.
UNASSIGNED: A significant relationship was found between the IL-6 rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.

The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.
This case-control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.
As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09-1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06-1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).
This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

OBJECTIVE: The present study aimed to investigate the potential association of VEGF-116G/A promoter polymorphism with esophageal cancer risk in North-West Indians and to perform a comprehensive meta-analysis of VEGF-116G/A polymorphism in Gastrointestinal Tract (GIT) cancers.
METHODS: A total of 679 DNA samples (333 esophageal cancer patients and 346 healthy controls) were genotyped for VEGF-116G/A polymorphism using Sanger sequencing. In silico analysis was carried out to predict the impact of VEGF-116G/A polymorphism on transcription factor binding sites. Ten studies including 2157 patients and 2307 controls on different GIT cancers were included in the meta-analysis.  Results: The AA genotype and A allele of VEGF -116G/A polymorphism was significantly associated with an increased risk of esophageal cancer. In silico analysis predicted that A allele of VEGF-116G/A polymorphism created new binding sites for STAT4, c-Ets-1 and Elk-1 transcription factors. The meta-analysis results showed that VEGF-116G/A polymorphism was associated with an increased risk of GIT cancer under the recessive and AA vs GG genetic model in the overall population. Stratification of the studies by ethnicity revealed an increased risk of GIT cancers in Asians under allele contrast, recessive, AA vs GG and AA vs AG model. Analysis based on cancer type revealed an increased risk of esophageal cancer under allele contrast, recessive, AA vs GG and AA vs AG comparison model and increased risk of oral cancer was observed under the allele contrast model and dominant model.
CONCLUSIONS: VEGF-116G/A polymorphism was associated with esophageal cancer risk in North- West Indians. The findings of the present meta-analysis showed a significant association of VEGF-116G/A polymorphism with GIT cancer risk.

UNASSIGNED: Recurrent miscarriage (RM), defined as two or more consecutive miscarriages prior to the 20th week of gestation is characterised by multifactorial aetiology. The prevalence of RM varies from 0.8% to 13.5% amongst women of reproductive age. The aetiological basis of RM has been traced to chromosomal, anatomic, hormonal and immunologic factors while half of the cases remain idiopathic.
UNASSIGNED: This study aimed to investigate the association of interleukin-10 (IL-10) polymorphisms with RM amongst the Indian population.
UNASSIGNED: The present study included a total of 414 individuals including RM women (n = 199) with two or more pregnancy losses and healthy women (n = 215) without any previous history of pregnancy loss were taken as the control group.
UNASSIGNED: Demographic features and reproductive history of women with RM and healthy women were taken. Genotype analysis of IL-10 polymorphisms rs1800872 and rs1800896 was performed using the polymerase chain reaction (PCR) restriction fragment length polymorphism and amplification mutation refractory system PCR, respectively.
UNASSIGNED: Student\'s t-test was used to compare the demographic features and reproductive history amongst both groups. Pearson\'s Chi-square was used to calculate the Hardy-Weinberg equilibrium, allelic and genotypic frequencies. All the statistical analyses were performed using the SPSS (version 21, IBM SPSS, NY, USA).
UNASSIGNED: Our results suggested that the genotypic and allelic frequency of rs1800872 polymorphism did not differ significantly between RM cases and control women (P = 0.07 and P = 0.23, respectively). The GG genotype (P = 0.007) and G allele (P = 0.003) of rs1800896 were significantly associated with an increased risk of RM. A statistically significant difference was also found for the distribution of genetic models (dominant and co-dominant model) between both groups for rs1800896. However, haplotype analysis revealed that none of the haplotypes provides a risk for the progression of RM.
UNASSIGNED: The study is the first of its kind from our region and provides baseline data on the genetics of RM.

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one\'s predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient\'s plasma promoted higher CD62p expression in healthy donors\' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

We are reporting on the utilization of high-throughput sequencing and different sequencing analysis tools to delineate identification of different isolates of the stripe rust fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Different approaches are shown: utilization of rDNA sequences and random sequences that may be very useful to make sure that isolates belong to Pst and to distinguished closely related isolates. Identification of unique/lost sequences could lead to the identification of effectors associated with specific isolates.