Allele Of Single Nucleotide Polymorphisms Research Articles

Abstract 7416: Prevalence of IL28B single nucleotide polymorphism Rs12979860 and cytomegalovirus (CMV) among allogeneic stem cell transplant in leukemia children

Abstract Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality among allogeneic stem cell transplant (allo-SCT) recipients especially in pediatric leukemia patients. IFN-λ family: interleukin (IL)-28A, -28B, and -29 and IFN-λ4. All have antiviral properties similar to IFN-α. In vivo, IFN-λs are mostly secreted by dendritic cells (DC) and macrophages. IL-28B signals through a heterodimeric receptor consisting of IL-28R1 chains and IL-10Rβ, hence inducing an antiviral state. It has been shown that screening allo-SCT recipients for the presence of defined polymorphisms in genes involved in the regulation and activation of innate and adaptive immune responses may help to predict their individual risk of viral infection and disease. Our study aims to investigate the prevalence of single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene among allo-SCT recipients and to investigate whether that SNP has any effect on the incidence rate and the features of active CMV infection in cancer children receiving stem cell transplantation. Thirty-five patients undergoing allo-SCT in 57357 children’s cancer hospital were included in the study (age range, 2-20 years). A total of thirty-five whole blood samples were collected. DNA Extraction from Blood Samples was performed by using ThermoScientific GeneJet genomic DNA purification kit, IL28B SNP Analysis L28B (rs12979860) genotyping was performed by RT-qPCR (Applied Biosystems TaqMan SNP genotyping assay) using QuantStudio ViiA7 system, and routine screening of CMV was performed once a week by real-time PCR (ViroGene real-time CMV quantification kit). The prevalence of single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene among allo-SCT in cancer children was as follows: C/C carriers were 34.3%, C/T carriers were 42.8% and T/T carriers were 22.8%, 37.1% of patients had one or more episodes of active CMV infection during the first 100 days following allo-SCT. Patients carrying the homozygous T allele had a shorter duration of initial active CMV infection than those carrying the homozygous or heterozygous C-allele. Also, Patients carrying the homozygous T allele show a lower magnitude of CMV DNA viral load within their initial episodes of CMV infection compared to the C/C and C/T groups. Data from the current study showed a protective effect of the homozygous T allele of IL28B SNP (rs12979860) against CMV infection in cancer patients undergoing allo-SCT, T/T carriers showed a lower incidence of active CMV infection episodes occurring within 100 days after allo-SCT, those episodes were shorter in duration and lower in magnitude compared to patients carrying C/C and C/T allele. These findings emphasize the potential for personalized risk assessment and management strategies in pediatric allo-SCT recipients based on IL28B SNP profiling. Citation Format: Mohamed A. Eltokhy, Israa Gamal, Omar A. Eltoukhy, Youssif Madney, Mohamed M. Farag, Tarek Mansour, Sanjay K. Srivastava, Sahar Radwan. Prevalence of IL28B single nucleotide polymorphism Rs12979860 and cytomegalovirus (CMV) among allogeneic stem cell transplant in leukemia children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7416.

Magnolol inhibits appetite and causes visceral fat loss through Growth/differentiation factor-15 (GDF-15) by activating transcription factor 4-CCAAT enhancer binding protein γ-mediated endoplasmic reticulum stress responses.

Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.

PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes.

PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes.

Comorbidities And Risk Factors For COVID-19 In A Group Of Iraqi Patients Confirmed By Real-Time PCR Test

Coronary artery disease (CAD) is a major global contributor to mortality and morbidity. Genetic susceptibility plays a significant role in its etiology, particularly when CAD occurs prematurely. However, the relationship between premature CAD (PCAD) and specific genetic polymorphisms in the Iraqi population is still unclear. This aim of this study to assess the relationship between the KALRN gene single nucleotide polymorphism (SNP) (rs9289231T>G) and the development of PCAD in Iraqi patients. It also assesses the potential of serum Kalirin protein levels as a biomarker for PCAD. The study included 92 participants divided into two groups. Polymerase chain reaction (PCR) was performed to detect the KALRN SNP (rs9289231T>G), and the PCR products were analyzed via Sanger sequencing. Kalirin protein serum levels were measured using the ELISA technique. An association with statistical significance was found between the frequencies of genotypes and alleles of the KALRN SNP (rs9289231T>G) among the study groups, following a dominant genetic model. There was also a relationship between the genotypes of the KALRN SNP and CAD severity. Kalirin serum levels were significantly elevated in participants with CAD and were associated with the KALRN SNP genotypes. The KALRN SNP (rs9289231T>G) is associated with premature CAD in the Iraqi population, and follows a dominant genetic model. Elevated Kalirin serum levels, linked to the presence of the mutant allele, may serve as a biomarker for early diagnosis of the disease.

Exploring genetic risk factors for β-cell deterioration in type 2 diabetes mellitus: Insights from longitudinal C-peptide analysis.

Exploring genetic risk factors for β-cell deterioration in type 2 diabetes mellitus: Insights from longitudinal C-peptide analysis.

Association of Insulin Receptor Substrate-1 Gly972Arg Polymorphism with Dyslipidemia in Iraqi Type 2 Diabetic patients: A case-control Study

Background: Diabetic dyslipidemia is a primary contributor to mortality from coronary artery disease (CAD). It is prevalent in diabetic patients and manifests as an elevation of triglyceride (TG) alongside reduced high-density lipoprotein (HDL) concentrations. Both genetic and environmental factors influence the onset of dyslipidemia in type 2 diabetes mellitus (T2DM). The current study aimed to evaluate the involvement of the IRS-1 Gly 972 Arg gene polymorphism in the development of dyslipidemia in type 2 Iraqi diabetics Methods: Two hundred type 2 Iraqi diabetics were recruited, 105 patients with dyslipidemia and 95 without. The IRS-1 gene was analyzed for Gly 972 Arg single nucleotide polymorphism (SNP) by PCR-RFLP. Results: The codominant models explored a significant (OR = 4.4, CI 95% = 1.4 – 13.9, P = 0.01) increase of carriers of the GA genotype in the group of diabetics with dyslipidemia compared to those without. The dominant models highlighted a significant (OR = 4.7, P = 0.008, CI 95% = 1.5 – 14.8) rise of carriers of the variant allele in the group of diabetics with dyslipidemia when compared with those of diabetic patients without. The distribution of the investigated phenotypes was analyzed in relevance to the genotypes of the dominant model (GA + AA vs GG). There were significant (P = 0.01 – 0.006) elevations of fasting serum glucose (FSG), glycosylated haemoglobin (HbA1c), TC, TG, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL), concentrations in carriers of the GA+ AA genotypes when compared with those of the GG genotypes. However, IRS-1 concentration was significantly (P = 0.04) decreased in the group of GA+AA carriers compared to those of the GG carriers. Conclusions: Type 2 Iraqi diabetics who carry the variant allele of the rs1801278 SNP of the IRS1 gene are fourfold more susceptible to dyslipidemia compared to those who have the wild allele. Moreover, metabolic changes are relevant to the analyzed SNP.

Association of IL10 gene polymorphism with the susceptibility to dengue and disease severity in a population with asymptomatic and symptomatic dengue.

Association of IL10 gene polymorphism with the susceptibility to dengue and disease severity in a population with asymptomatic and symptomatic dengue.

The Association Between the rs2200733 SNP and Atrial Fibrillation Among Arabs: A Study from Jordan.

Atrial fibrillation (AFib) is a common disorder featured by an irregular and fast heartbeat. The etiology of AFib is complex and involves genetic and environmental factors. The rs2200733 single nucleotide polymorphism (SNP) is located in close proximity to the promoter of paired-like homeodomain transcription factor 2 (PITX2) which plays a role in heart development. In this study, the association between the rs2200733 SNP and AFib was examined in the Jordanian population. The study included 450 subjects (274 controls and 176 patients with AFib). Patients were recruited from King Abdullah University Hospital based on the European Society of Cardiology criteria. The rs2200733 SNP was genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. The mutant T allele of the rs2200733 SNP was common in the studied population with a frequency of 19%. The T allele and CT/TT genotypes were prevalent among patients with AFib compared with the controls (P<0.05, OR [CI]: 1.65 [1.12-2.43]). In addition, body mass index, diabetes, and hypertension were found to be associated with AFib risk. The rs2200733 SNP was associated with AFib among Jordanian patients. The mutant T allele of the rs2200733 SNP might increase the risk of AFib.

CASR, CLDN 14, ALPL & SLC34A1 genes are associated with the risk of nephrolithiasis in Egyptian children.

CASR, CLDN 14, ALPL & SLC34A1 genes are associated with the risk of nephrolithiasis in Egyptian children.

E-cadherin Single Nucleotide Variants Are Associated with Increasing Susceptibility to Periodontitis.

To investigate the association of E-cadherin single nucleotide polymorphisms (SNPs) with periodontitis and the potential of these SNPs for identifying susceptibility to periodontitis. Periodontal clinical parameters were recorded followed by collecting venous blood for DNA extraction. Polymerase chain reaction was used to amplify target segments of the E-cadherin gene. Determination of the genotype and allele frequencies was performed using Sanger sequencing. All statistical analyses were performed using GraphPad Prism (version 9) using a statistically significant difference of p < 0.05. A total of 207 participants were recruited into two groups of healthy controls (n = 105) and cases diagnosed with periodontitis stage 2 or 3, grade B or C (n = 102). Analyses indicated that the genotypes and alleles of rs3743674 and rs5030625 E-cadherin SNPs were significantly associated with periodontitis. Results from a binary regression model suggested that the presence of these SNPs may indicate susceptibility to periodontitis and increase the rate of progression. Linkage disequilibrium analysis indicated that E-cadherin variants rs3743674 and rs5030625, and rs10272115 and rs16260 were correlated in a nonrandom manner (r 2 = 0.638 and 0.495, respectively). E-cadherin gene variants, rs3743674 and rs5030625, were associated with the periodontitis phenotype. These biomarkers may identify individuals susceptible to periodontitis and the rate of disease progression.

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.

Diabetes Risk Allele of Transcription Factor 7-like 2 (TCF7L2) Polymorphisms is Associated with Higher Glucagon-like Peptide 1 (GLP1) and Lower Insulin Secretion

BACKGROUND: The most influential susceptible gene associated with diabetes, transcription factor 7-like 2 (TCF7L2), has been observed in diverse populations. TCF7L2 influences type 2 diabetes risk through glucagon-like peptide 1 (GLP1) production. The presence of risk allele of TCF7L2 leads to the alteration of gene expression in pancreatic beta cells; however, how the mechanism is related with GLP1 remains unclear. This study was conducted to explore the variations of GLP1 increment and insulin secretion between individuals with and without diabetes risk allele of single nucleotide polymorphisms (SNPs) in TCF7L2.METHODS: A cross-sectional analytic study was conducted involving individuals subjects who harbored known variants of SNPs in the TCF7L2: heterozygote or mutant of rs12255372 (GT or TT), rs7903146 (CT or TT), rs10885406 (AG or GG); as well as control subjects with wild type of rs12255372 (GG), rs7903146 (CC), and rs10885406 (AA). Anthropometric parameters, blood glucose, insulin, and GLP1 were measured; and homeostasis model assessment-beta cell (HOMA-%B) index was calculated.RESULTS: The GLP1 increment response was higher in subjects carrying the diabetes risk allele (0.34±0.80 ng/mL) than those with the wild type (-0.04±0.57 ng/mL) (p=0.041). The HOMA-%B was reduced in subjects carrying the diabetes risk allele (71.64±24.72) than those with the wild type (103.23±68.00) (p=0.011). Among individuals carrying the diabetes risk allele, the likelihood of GLP1 increment with high response was twice as high (p=0.007), while the occurrence of low HOMA-%B was 1.47 more frequent (p=0.011).CONCLUSION: TCF7L2 polymorphisms were associated with the GLP1 increment response and reduced HOMA-%B, which might be potentially contributing to GLP1 resistance in patients with diabetes risk factors.KEYWORDS: diabetes risk, TCF7L2, GLP1, HOMA-%B

ApaI Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn’s Disease

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn’s disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease’s location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts.

MicroRNA‑24 alleviates colorectal cancer progression via a rs28382740 single nucleotide polymorphism in the long noncoding region of X‑linked inhibitor of apoptosis protein.

Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Recurrence is associated with the poor survival of patients with CRC. Targeted therapy and precision medicine for recurrent CRC may improve the clinical outcome. Therefore, finding biomarkers that can detect CRC early, assess its prognosis and survival, and predict its treatment response is key to improving the clinical prognosis. The aim of this study was to assess CRC recurrence by analyzing molecular differences using postoperative specimens. Whole-exome sequencing was first used to evaluate the molecular differences in CRC tissues from patients with recurrent disease, and the results were then verified with tissue array methods. The regulation of single nucleotide polymorphisms (SNPs) in long noncoding regions of interest was analyzed in the presence of target microRNAs (miRs) using luciferase assays. The results demonstrated that in patients with recurrent CRC, the G allele was mainly detected at the rs28382740 SNP in the 3'-untranslated region of the X-linked inhibitor of apoptosis (XIAP)-encoding gene. From the tissue arrays, 60% (3/5) of patients with the G allele of the rs28382740 SNP were diagnosed with CRC recurrence, whilst only 10% (1/10) of patients without the G allele had recurrent CRC (P=0.077). Furthermore, XIAP levels were high in non-CRC (50%; 2/4) and CRC (75%; 3/4) tissues of patients with recurrent disease and CRC (54.5%; 6/11) tissues of patients without recurrent disease. However, but only 9.1% (1/11) of non-CRC tissues of nonrecurrent patients had significantly high XIAP expression levels (P=0.022). Using a luciferase assay, it was demonstrated that miR-24s (miR-24-1-5p and miR-24-2-5p) targeting the rs28382740 SNP reduced XIAP levels in CRC cells with rs28382740 SNP genotype G. These results indicate that apoptosis-related proteins, such as XIAP, may be therapeutic targets or biomarkers for tumor development. The data from the present study support an inhibitory effect of miR-24s on XIAP expression. However, this inhibitory potency depends on the rs28382740 SNP genotype and may alleviate CRC progression by regulating the expression of XIAP.

Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to C8B rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158–1.590); p: 0.00016] and MFG-E8 rs2015495 [OR (95% CI): 1.313 (1.134–1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.

Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma.

This study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) in the CD44 gene, specifically in the 3'UTR region (rs13347) and intronic region (rs187115), on the cell surface expression of CD44 protein and the risk of development of head and neck squamous cell carcinoma (HNSCC). The study involved analysis of 85 samples and 85 healthy controls. Immunohistochemistry (IHC) and flow cytometry were used to assess cell surface protein expression using CD44 antibody. DNA from formalin-fixed paraffin-embedded tissue sections was isolated and amplified using targeted primers. Sanger sequencing of the resultant amplified products was performed to determine the genotypes of the CD44 rs13347 and rs187115 SNPs. GTEx and RegulomeDB were queried to evaluate the genotypic effects of these variants on target gene expression and regulation. A comparison between patients with HNSCC and healthy controls revealed a significant association between CD44 rs13347 and an increased risk of HNSCC in all the analyzed models, especially the TT genotype showed a significantly higher risk with an odds ratio of 8.69 (95% CI, 2.35 to 32.09; P = .0003). However, no significant association was found between CD44 rs187115 and HNSCC in any of the models analyzed (all P > .05). Other notable findings included significant associations between CD44 rs13347 genotype and age (P = .031), number of CD44-positive tumor cells (P = .049), CD44 staining intensity (SI; P = .039), and CD44 immunoreactivity score (IRS) status (P = .019). The T allele and homozygous TT genotype of CD44 rs13347 SNP were associated with increased susceptibility to HNSCC and decreased proportion of CD44-positive tumor cells, low SI, and reduced IRS.

Polymorphisms in the genes encoding RLR and TLR3 and CMV DNAemia in subjects coinfected with human immunodeficiency virus and cytomegalovirus

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33–4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-β concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

Transcriptomic Insights into the Atrial Fibrillation Susceptibility Locus near the MYOZ1 and SYNPO2L Genes.

Genome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 (MYOZ1) and synaptopodin 2-like (SYNPO2L) transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels. Chromatin marks were used to suggest candidate regulatory SNPs in this region. Protein amino acid changes were examined for predicted functional consequences. Transfection of MYOZ1 and two SYNPO2L isoforms were performed to localize their encoded proteins in cardiomyocytes derived from stem cells. We identified one MYOZ1 transcript isoform and four SYNPO2L transcript isoforms, two of which encode proteins, while the other two encode long noncoding RNAs (lncRNAs). The risk allele of the strongest AF susceptibility SNP on chromosome 10q22 is associated with decreased MYOZ1 expression and increased expression of the two SNYPO2L lncRNA isoforms. There are many SNPs co-inherited with the top AF-associated SNP due to linkage disequilibrium (LD), including rs11000728, which we propose as the MYOZ1 regulatory SNP, confirmed by reporter gene transfection. In addition, this LD block includes three missense SNPs in the SYNPO2L gene, with the minor protective haplotype predicted to be detrimental to protein function. MYOZ1 and both protein isoforms of SYNPO2L were localized to the sarcomere. This is a complex locus with the potential for several SNPs in a haplotype to alter AF susceptibility by opposing effects on MYOZ1 and SYNPO2L lncRNA expression, along with effects on SYNPO2L protein function.

&lt;i&gt;CDKN2B-AS1&lt;/i&gt; polymorphism rs1333049 is associated with advanced carotid artery atherosclerosis in a Slovenian population

Several studies have reported an association between the 9p21 region in the human genome and atherosclerosis. The rs1333049 polymorphism is a single nucleotide polymorphism (SNP) in CDKN2B-AS1, located in the 9p21 region. The aim of our study was to investigate the association between the rs1333049 polymorphism and advanced carotid atherosclerosis, as well as its effect on CDKN2B expression in endarterectomy sequesters. In our case-control study, we included 881 participants, divided into two groups. The case group comprised 308 participants with advanced atherosclerosis of the internal or common carotid artery (stenosis &gt; 75 %) who underwent a revascularization procedure. The control group included 573 participants without hemodynamically significant carotid atherosclerosis. We analyzed the rs1333049 polymorphism using the StepOne real-time polymerase chain reaction (PCR) and TaqMan SNP genotyping assay. We found a statistically significant association according to the co-dominant (P=0.014, OR=3.29, 95% CI: 1.32-8.91, and P=0.015, OR=2.50, 95% CI: 1.22-5.37) and dominant (P=0.006, OR=2.74, 95% CI: 1.36-5.71) models. We performed immunohistochemical analysis of CDKN2B expression on 26 endarterectomy sequesters. The C allele of rs1333049 was associated with a lower numerical area density of CDKN2B-positive cells in atherosclerotic plaques. In conclusion, the C allele of the rs1333049 SNP is associated with an increased risk of developing advanced carotid atherosclerosis and lower CDKN2B expression in the plaques.

SeqSNP-Based Targeted GBS Provides Insight into the Genetic Relationships among Global Collections of Brassica rapa ssp. oleifera (Turnip Rape).

Turnip rape is a multi-purpose crop cultivated in temperate regions. Due to its ability to fit into crop rotation systems and its role as a food and feed source, spring-type turnip rape cultivation is on the rise. To improve the crop's productivity and nutritional value, it is essential to understand its genetic diversity. In this study, 188 spring-type accessions were genotyped using SeqSNP, a targeted genotyping-by-sequencing method to determine genetic relationships between various groups and assess the potential effects of mutations within genes regulating major desirable traits. Single nucleotide polymorphism (SNP) alleles at six loci were predicted to have high effects on their corresponding genes' functions, whereas nine loci had country/region-specific alleles. A neighbor-joining cluster analysis revealed three major clusters (I to III). About 72% of cluster-I accessions were of Asian origin, whereas 88.5% of European accessions and all North American accessions were placed in cluster-II or cluster-III. A principal coordinate analysis explained 65.3% of the total genetic variation. An analysis of molecular variance revealed significant differentiation among different groups of accessions. Compared to Asian cultivars, European and North American cultivars share more genetic similarities. Hence, crossbreeding Asian and European cultivars may result in improved cultivars due to desirable allele recombination. Compared to landraces and wild populations, the cultivars had more genetic variation, indicating that breeding had not caused genetic erosion. There were no significant differences between Swedish turnip rape cultivars and the NordGen collection. Hence, crossbreeding with genetically distinct cultivars could enhance the gene pool's genetic diversity and facilitate superior cultivar development.