Single Nucleotide Polymorphisms In Genes Research Articles

Oxytocin pathway gene variation and corticostriatal resting-state functional connectivity

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000). Our findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. Empirical evidence has linked the GG genotype at OXT rs4813627 with a behavioral tendency of insensitivity to others. These results inform the neural mechanisms by which oxytocin-related genetic factors can influence social behavior.

Impact of 5' Near Gene Variants of Mannose Binding Lectin (MBL2) on Breast Cancer Risk.

The immune system plays a bifaceted role in tumour development through modulation of inflammation. MBL binds to damage-associated molecular patterns and induces inflammation through the activation of complement pathway. Dysregulated inflammation plays a major role in breast cancer pathogenesis, thereby suggesting its contribution towards breast cancer risk. Literature asserts single-nucleotide polymorphisms (SNPs) modulating serum MBL levels. Therefore, studying MBL2 SNPs in breast cancer might provide valuable insight in the disease pathogenesis. The present case-control association study aimed to elucidate the association between MBL2 5' near gene SNPs and breast cancer risk. Breast cancer patients were recruited from Government Medical College, G.N.D. Hospital, Amritsar. The age- and gender-matched genetically unrelated healthy individuals, from adjoining regions, with no history of malignancy up to three generations were recruited as controls. The SNPs of MBL2 from the 5' near gene region with putative functional significance were selected based upon the in silico analysis and literature review. The genotypic, allelic and haplotype frequencies for the studied variants were assessed and compared in the study participants by ARMS-PCR and PCR-RFLP. No difference in allelic, genotypic and haplotype frequencies was reported for rs7096206, rs7084554 and rs11003125 in both the participant groups. rs7084554 (CC) was found to confer risk towards hormone receptor-positive breast cancer. An intermediate LD was observed between rs7084554 and rs11003125. The study reports association between MBL2 variant (rs7084554) and hormone receptor-positive breast cancer risk. Further research in this direction might validate the findings.

Integrative prediction model for radiation pneumonitis incorporating genetic and clinical-pathological factors using machine learning

PurposeWe aimed to develop a machine learning-based prediction model for severe radiation pneumonitis (RP) by integrating relevant clinicopathological and genetic factors, considering the associations of clinical, dosimetric parameters, and single nucleotide polymorphisms (SNPs) of genes in the TGF-β1 pathway with RP. MethodsWe prospectively enrolled 59 primary lung cancer patients undergoing radiotherapy and analyzed pretreatment blood samples, clinicopathological/dosimetric variables, and 11 functional SNPs in TGFβ pathway genes. Using the Synthetic Minority Over-sampling Technique (SMOTE) and nested cross-validation, we developed a machine learning-based prediction model for severe RP (grade ≥ 2). Feature selection was conducted using four methods (filtered-based, wrapper-based, embedded, and logistic regression), and performance was evaluated using three machine learning models. ResultsSevere RP occurred in 20.3 % of patients with a median follow-up of 39.7 months. In our final model, age (>66 years), smoking history, PTV volume (>300 cc), and AG/GG genotype in BMP2 rs1979855 were identified as the most significant predictors. Additionally, incorporating genomic variables for prediction alongside clinicopathological variables significantly improved the AUC compared to using clinicopathological variables alone (0.822 vs. 0.741, p = 0.029). The same feature set was selected using both the wrapper-based method and logistic model, demonstrating the best performance across all machine learning models (AUC: XGBoost 0.815, RF 0.805, SVM 0.712, respectively). ConclusionWe successfully developed a machine learning-based prediction model for RP, demonstrating age, smoking history, PTV volume, and BMP2 rs1979855 genotype as significant predictors. Notably, incorporating SNP data significantly enhanced predictive performance compared to clinicopathological factors alone.

Pharmacogenomic Polygenic Model of Clopidogrel Predicts Recurrent Ischemic Events in Chinese Patients With Coronary Artery Disease

Patients with coronary artery disease (CAD) need to take antiplatelet drugs regularly in order to prevent thrombosis; however, there is existing inter-individual variability in drug response. Pharmacogenomic studies indicate that drug response may also be influenced by genetic variants, and multiple genetic variants may work together. We assumed that patients carrying more risk alleles might have a worse clopidogrel drug response and that a polygenic model integrated different single variants might have the potential to explain clopidogrel drug response variability better. We aimed to investigate whether the polygenic model could be used to predict clopidogrel drug response. A total of 935 CAD patients were enrolled in the study. We investigated the association between 19 clopidogrel-related single-nucleotide polymorphisms (SNPs) and the incidence of recurrent ischemic events. Additionally, a polygenic model was constructed to assess the risk of ischemic events. There were only 2 SNPs of CYP2C8 gene (rs1934980 and rs17110453) that were nominally associated with incidence of recurrent ischemic events. We constructed a polygenic model integrated with 6 clopidogrel-related SNPs. When compared with patients carrying 6 or fewer risk alleles, patients with 7 or more risk alleles had a higher risk of ischemic events (hazard ratio = 1.87; P = 0.04). The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.

A multi-AS-PCR-coupled CRISPR/Cas12a assay for the detection of ten single-base mutations

Single-nucleotide polymorphism (SNP) detection is critical for diagnosing diseases, and the development of rapid and accurate diagnostic tools is essential for treatment and prevention. Allele-specific polymerase chain reaction (AS-PCR) is widely used for detecting SNPs with multiplexing capabilities, while CRISPR-based technologies provide high sensitivity and specificity in targeting mutation sites through specific guide RNAs (gRNAs).In this study, we have integrated the high sensitivity and specificity of CRISPR technology with the multiplexing capabilities of AS-PCR, achieving the simultaneous detection of ten single-base mutations. As for Multi-AS-PCR, our research identified that competitive inhibition of primers targeting the same loci, coupled with divergent amplification efficiencies of these primers, could result in diminished amplification efficiency. Consequently, we adjusted and optimized primer combinations and ratios to enhance the amplification efficacy of Multi-AS-PCR. Finally, we successfully developed a novel nested Multi-AS-PCR-Cas12a method for multiplex SNPs detection. To evaluate the clinical utility of this method in a real-world setting, we applied it to diagnose rifampicin-resistant tuberculosis (TB). The limit of detection (LoD) for the nested Multi-AS-PCR-Cas12a was 102 aM, achieving sensitivity, specificity, positive predictive value, and negative predictive value of 100 %, 93.33 %, 90.00 %, and 100 %, respectively, compared to sequencing.In summary, by employing an innovative design that incorporates a universal reverse primer alongside ten distinct forward allele-specific primers, the nested Multi-AS-PCR-Cas12a technique facilitates the parallel detection of ten rpoB gene SNPs. This method also holds broad potential for the detection of drug-resistant gene mutations in infectious diseases and tumors, as well as for the screening of specific genetic disorders.

The association between endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms and the risk of psoriasis and psoriatic arthritis in Egyptians.

Psoriasis (Ps) is a disorder attributed to the immune system that involves inflammation of the skin and joints. Psoriasis is a multifactorial disorder in which genetic factors represent about 70% of the disease risk. This study aims to establish the correlation between the ERAP2 gene's single nucleotide polymorphisms (SNPs) rs2910686 and rs2248374 with the susceptibility to Ps and/or psoriatic arthritis (PsA) among the Egyptian population. Genotyping of ERAP2 gene SNPs (rs2910686 and rs2248374) in 120 psoriatic patients with and without arthritis and 100 controls was done using real-time PCR. The genotype frequency and distribution of the ERAP2 SNP (rs2910686 and rs2248374) were in Hardy-Weinberg equilibrium (HWE). For rs2910686, the TC and CC genotypes and C allele frequency were significant risk factors for PsA compared to the controls (OR = 5.708, OR = 10.165, and OR = 4.282, respectively). They also were significant risk factors for Ps compared to the controls (OR = 5.165, OR = 5.040, and OR = 3.258, respectively). For rs2248374, the AG genotype significantly increased the risk of PsA (OR = 2.605) and Ps (OR = 3.768) compared to controls. The AG genotype was significantly related to the risk of Ps (OR = 3.369) G allele with PsA (OR = 1.608) and Ps (OR = 1.965) compared to controls. In Egyptian individuals, the ERAP2 gene polymorphisms (rs2248374 and rs2910686) may contribute genetically to the pathophysiology of psoriasis and PsA.

IL-10 polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population

Background and aimAs the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (−1082A/G (rs1800896) and −592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians. MethodsIL-10 gene SNPs were analyzed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP. ResultsFor the IL-10 -1082A/G SNP, the comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA + AG: OR [95%CI] = 0.44 [0.21–0.93], p = 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA + GG) and high susceptibility (OR [95%CI] = 1.65 [1.02–2.63], p = 0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI] = 0.18 [0.04–0.72], p = 0 0.01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI] = 5.16 [1.31–23.26], p = 0.02). Furthermore, the codominant model (AG vs. AA + GG) doubled the risk of rectum cancer (OR [95%CI] = 1.98 [1.07–3.70], p = 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA + CC) has a protective effect against the development of CRC (OR [95%CI] = 0.59 [0.36–0.94], p = 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (−1082G and −592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI] = 0.51 [0.32–0.80], p = 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI] = 0.35 [0.14–0.85], p = 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p = 0.01). This association was also observed in the colon cancer subgroup (Log-rank: p = 0.001). ConclusionOur findings provide preliminary indications that the −1082A/G and −592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.

Single-Nucleotide Polymorphisms in WNT Genes in Patients with Non-Syndromic Orofacial Clefts in a Polish Population.

Non-syndromic orofacial cleft (OFC) is the most common facial developmental defect in the global population. The etiology of these birth defects is complex and multifactorial, involving both genetic and environmental factors. This study aimed to determine if SNPs in the WNT gene family (rs1533767, rs708111, rs3809857, rs7207916, rs12452064) are associated with OFCs in a Polish population. The study included 627 individuals: 209 children with OFCs and 418 healthy controls. DNA was extracted from saliva for the study group and from umbilical cord blood for the control group. Polymorphism genotyping was conducted using quantitative PCR. No statistically significant association was found between four variants and clefts, with odds ratios for rs708111 being 1.13 (CC genotype) and 0.99 (CT genotype), for rs3809857 being 1.05 (GT genotype) and 0.95 (TT genotype), for rs7207916 being 0.86 (AA genotype) and 1.29 (AG genotype) and for rs12452064 being 0.97 (AA genotype) and 1.24 (AG genotype). However, the rs1533767 polymorphism in WNT showed a statistically significant increase in OFC risk for the GG genotype (OR = 1.76, p < 0.001). This research shows that the rs1533767 polymorphism in the WNT gene is an important risk marker for OFC in the Polish population.

Genetic aspects associated with increased risk of developing atrial fibrillation

Abstract Atrial Fibrillation (AF) is the most common sustained arrhythmia in clinical practice with increasing prevalence and association with increased morbidity and mortality. Studies have suggested a greater contribution of the genetic factor to the etiopathogenesis of arrhythmia, which could indicate up to 40% more risk for the individual who has a family member with the arrhythmia, and later in the form of single nucleotide polymorphisms (SNPs). Objective To verify the association of polymorphisms in the PITX2, HCN4, CAV1 and KCNN3 genes with the occurrence of AF. Method The study is cross-sectional with group comparison, prospective with a quantitative approach. 505 randomly selected subjects were included (357 cases and 148 controls). The real-time PCR methodology was used, using the TAQMAN® system (Thermo scientific, CA, USA). Result The sample was matched by sex and age. The most common type of AF was permanent (69%) followed by paroxysmal (23%). When comparing the groups selected for CAV1, statistical significance was found for AA vs AG genotypes (p 0.003; OR= 2.2; CI 1.29-3.7). For the HCN4 gene allele and genotypes A vs G (p 0.024; OR= 0.66; CI 0.47-0.9) and AA vs AG (p 0.014, OR= 0.57; CI 0.37-0.88), respectively. Regarding the comparison of the dominant and recessive genetic model of each gene, the following models/genes presented statistical significance: in the genotypic model of the CAV1 gene (AA vs AG vs GG) p 0.013, as well as the same model applied to the HCN4 gene (AA vs AG vs GG) (p 0.03); when comparing the dominant models, the HCN4 gene (AA vs AG/GG) presented (p 0.01; OR=0.58; 95% CI 0.38 – 0.88), with the recessive model of the CAV1 gene (AA vs AG/GG) with (p 0.008; OR=2.0; 95% CI: 1.19 – 3.34). Regarding allelic associations between the two groups, a greater chance of susceptibility to developing AF was observed in patients who had the "G" allele (25.6%; p 0.024; OR= 0.66, CI 0.47-0.9) in the HCN4 gene polymorphism. Polymorphisms in the CAV1 (rs3807989) and HCN4 (rs7164883) genes were also included in the multivariate analysis with maintenance of the risk factor for AF. However, only HCN4 rs7164883 showed statistical significan, thus showing it to be an independent variable regarding the probability of the patient with this polymorphism presenting AF. The present study showed a significant association with a greater chance of susceptibility to developing atrial fibrillation in patients with a polymorphism in the CAV1 gene (rs3807989) in a univariate and multivariate model and for patients with the HCN4 gene SNP (rs7164883). Conclusion Therefore, the results revealed an association between the HCN4 gene polymorphism rs7164883 and susceptibility to the development of AF, suggesting that the presence of the G allele may be one of the genetic factors related to the arrhythmia. The CAV1 rs3807989 gene polymorphism also seemed to suggest a risk for the development of AF, also relating the G allele.

MiRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population

The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005–0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00–2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22–181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32–3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = −1.07), and miR-143 (Log2FC = −1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.

Novel associations between MTDH gene polymorphisms and invasive ductal breast cancer: a case–control study

ObjectiveTo reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC).Patients and methodsA case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model.ResultsAmong the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk.ConclusionIn this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

P-556 Genetic variation in genes related to folliculogenesis and steroidogenesis in Caucasian and Asian women: Baby steps towards a pharmacogenetic approach in assisted reproductive techniques

Abstract Study question What is the impact of single nucleotide polymorphisms (SNPs) in genes related to the folliculogenesis and steroidogenesis on ovarian response to stimulation? Summary answer SMAD2 rs13381619 and COMT rs4680 variants are associated with the follicular output rate (FORT). What is known already The prediction of ovarian response (OR) is crucial for an optimal and individualized management. Despite the good accuracy of ovarian reserve markers in the prediction of OR, a proportion of patients are unexpected hypo-responders. Therefore, a link between OR and individual genotype has been suggested. However, the available evidence is limited by small sample sizes and heterogeneous study designs, including patients with different profiles and allowing for dose adjustments during treatment. Our aim was to analyze the association between SNPs in genes related to folliculogenesis and steroidogenesis and OR in an ethnic diverse population treated with the same fixed-dose protocol. Study design, size, duration This is a secondary analysis of a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium, and Spain (168 from Europe and 200 from Asia) recruited from 11/2016-06/2019. The study included predicted normal responders &amp;lt;38 years old undergoing their first or second ovarian stimulation (OS) cycle. All patients underwent OS in an antagonist protocol with a fixed daily dose of 150 IU rFSH until triggering. Participants/materials, setting, methods First, an interactome was developed using “FSHR” and “LHCGR” as keyword imputed in the Homo sapiens STRING database for protein network analysis. Genetic information from sixty-eight final SNPs involved in the folliculogenesis and steroidogenesis was obtained and used for clustering analysis. Secondly, genotype-phenotype analysis was performed. The prevalence of hypo-responders (&amp;lt;10 oocytes retrieved), number of oocytes retrieved, FORT and follicle to oocyte index (FOI) were compared between different SNPs genotypes. Main results and the role of chance Clustering analysis revealed four distinct genetic clusters according to the selected SNPs related to folliculogenesis and steroidogenesis. Principal component analysis (PCA) was used to display individuals’ distribution according to the fertility centre, resulting in an obvious distribution according to ethnicity. However, PCA failed to demonstrate a clinically significant association between our interactome and the outcomes of interest. We further refined our SNP panel by categorizing SNPs according to their physiological pathway and analyzed their individual impact on OR. Following multivariable linear regression adjusting for patient’s age, Anti-Mullerian hormone (AMH), duration of stimulation and ethnicity, SMAD2 rs13381619 genotype GC (estimated mean difference (EMD) 11.57, 95% Confidence interval (CI) 2.66-20.49), and COMT rs4680 genotype AA (EMD 18.31, 95% CI 4.91-31.72) were associated with improved FORT. No impact of the studied polymorphisms was found on the prevalence of hypo-response, number of oocytes retrieved nor FOI. Limitations, reasons for caution The study was performed in young women with a normal ovarian reserve to eliminate biases related to age-related fertility decline, precluding the extrapolation of the results to other populations. Moreover, the low prevalence of some genotypes might have limited the analysis of some of the included variants. Wider implications of the findings Our findings confirm the variation of SNPs prevalence according to ethnic diversity, highlighting the importance of the intercontinental design of our study. Moreover, a novel association between SMAD2 and COMT variants and OR was reported, opening new opportunities for further pharmacogenetics studies and paving the way towards personalized medicine. Trial registration number Not applicable

Detection of Toll like Receptor 2 Single Nucleotide Gene Polymorphism in Psoriasis

Detection of Toll like Receptor 2 Single Nucleotide Gene Polymorphism in Psoriasis

Identifying Oncogenic Missense Single Nucleotide Polymorphisms in Human SAT1 Gene Using Computational Algorithms and Molecular Dynamics Tools.

The human SAT1 gene encodes spermidine/spermine N1-acetyltransferase 1 (SSAT1), a regulatory biological catalyst of polyamine catabolism. Numerous essential biological processes, such as cellular proliferation, differentiation, and survival, depend on polyamines like spermidine and spermine. Thus, SSAT1 is involved in key cellular activities such as proliferation and survival of cells and mediates various diseases including cancer. A plethora of studies established the involvement of missense single nucleotide polymorphisms (SNPs) in numerous pathological conditions due to their ability to adversely affect the structure and subsequent function of the protein. To date, an in silico study to identify the pathogenic missense SNPs of the human SAT1 gene has not been accomplished yet. This study aimed to filter the missense SNPs that were functionally detrimental and pathogenic. The rs757435207 (I21N) was ascertained to be the most deleterious and pathogenic by all algorithmic tools. Stability and evolutionary conservation analysis tools also stated that I21N variant decreased the stability and was located in the highly conserved residue. Molecular dynamics simulation revealed that I21N caused substantial alterations in the conformational stability and dynamics of the SSAT1 protein. Consequently, the I21N variant could disrupt the native functional roles of the SSAT1 enzyme. Therefore, the I21N variant was identified and concluded to be an oncogenic missense variant of the human SAT1 gene. Overall, the findings of this study would be a great directory of future experimental research to develop personalized medicine.

Targeted Obesity Genes Single Nucleotide Polymorphisms, Diet, Lifestyles, and Obesity Indices: Nutrigenetics as a Predictive Model

Targeted Obesity Genes Single Nucleotide Polymorphisms, Diet, Lifestyles, and Obesity Indices: Nutrigenetics as a Predictive Model

Relationship between Selected SNPs (g.16024A/G, g.16039T/C and g.16060A/C) of the FASN Gene and the Fat Content and Fatty Acid Profile in the Milk of Three Breeds of Cows.

Fat is an important energy and nutritional component of milk and consists of fatty acids. FASN (fatty acid synthase) is an enzyme that regulates the synthesis of fatty acids in the milk and meat of cattle. It was hypothesized that knowing the relationships between the genotypes of the tested single nucleotide polymorphisms (SNPs) and the content of fat and specific fatty acids would make it possible to improve milk quality in the selection process during cattle breeding. This study aimed to analyze the relationships of SNPs (g.16024A/G, g.16039T/C) of the FASN gene and their genotypes with the fat and fatty acid content of the milk of the following breeds: Polish Red-White (ZR), Polish Red (RP), and Polish Holstein-Friesian Red-White (RW). The SNP g.16060A/C was included in the study, although its effect on the fat composition of cow's milk has not yet been widely studied. Milk was obtained during test milkings. SNP genotyping was performed using the real-time PCR (HRM) method. The milk from ZR and RP cows was more often characterized by a more favorable fatty acid profile than the milk from RW cows. This information can be used by cattle breeders and consumers of so-called functional food.

Relationship Between Cytotoxic T-Lymphocyte-associated Antigen-4: Programmed Death-1 Genes Polymorphisms and Susceptibility to Pediatric B-Cell Acute Lymphoblastic Leukemia.

Programmed death-1 (PD1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have a vital role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PD1 and CTLA4 have been reported to be associated with susceptibility to certain autoimmune diseases and cancers. The potential association between SNPs in these immune checkpoint genes and risk of acute lymphoblastic leukemia (ALL) still unclear. The aim of this study is to clarify the effect of PD1 and CTLA4 SNPs on the risk of developing ALL and the prognosis of the disease. The study was performed on 100 pediatric B-ALL patients and 100 controls. The PD1 and CTLA4 SNPs were examined by RFLP technique. The study revealed that CTLA4 (rs11571316) was associated with high risk of B-ALL developments OR 1.492 (CI: 1157 to 1924) ( P =0.002). PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission ( P =0.007). PD1 (rs36084323) A allele were associated with protective effect against relapse ( P =0.008). CTLA4 and PD1 genotypes did not have significant impact on B-ALL patients outcome. The current study displayed for the first time that genetic variations of the CTLA-4, was associated with susceptibility to B-ALL and that PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission, while PD1 (rs36084323) A allele was associated with protective effect against relapse.

A longitudinal population-based study identifies THBS2 as a susceptibility gene for intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common degenerative disease associated with ageing. Additionally, IDD is recognized as one of the leading causes of low back pain and disability in the working-age population and is the first step in the process leading to degenerative spinal changes. However, the genetic factors and regulatory mechanisms of IDD remain unknown. Therefore, we selected eight single nucleotide polymorphisms of genes to reveal the progression of IDD in a 7-year longitudinal study of the general population in Japan. IDD was evaluated in the Wakayama Spine Study (WSS), which is a population-based cohort study. Overall, 574 participants from the general population cohort who underwent whole spine magnetic resonance imaging and provided clinical information were included in this longitudinal survey. The progression of IDD was affected only by THBS2 at the lumbar region, T12-L1 (p = 0.0044) and L3-4 (p = 0.0045). The significant interaction between THBS2 and age with IDD negatively affected the thoracic spines and passively influenced both the thoracolumbar junction and thoracic spines. The higher progression per year of Pfirrmann's score was rapid in young people with age; however, this decelerated the IDD progression per year in different ages. Our longitudinal study found the genes associated with IDD progression and that genetic factors' impact on IDD differs depending on disc level and age.

Alterations in methylation and SNPs of OPRM1 gene show lack of association with heroin (nyaope) consumption in South African males of African ancestry

Nyaope is a highly addictive heroin derivative that elicits its effects via the -opioid receptor. Gene mutations and (cytosine-phospho-guanosine) CpG methylation, alter the function of the -opioid receptor gene (OPRM1) and protein. The single nucleotide polymorphisms (SNPs) rs1799971 (118 A&gt;G) and intronic rs3778150 (T&gt;C) in the OPRM1 have previously been associated with heroin use. The SNP rs1799971 can influence methylation levels of OPRM1 and alter mRNA and protein expression. This study compared the degree of OPRM1 methylation and allele frequency of SNPs rs1799971 and rs3778150 in black South African male nyaope users (n=200) to age-and gender-matched controls (n=55).DNA was extracted from whole blood samples, and analysed by methylation-specific PCR and sequencing to determine methylation frequencies across 29 CpGs within the OPRM1promoter gene region. SNPsrs1799971 (118 A&gt;G) and rs3778150 (T&gt;C) were assessed using SNP genotyping Taqman assays.Using a positive methylation assignment method, most CpGs were significantly more unmethylated in nyaope users than in controls. Using a partial methylation assignment method, most CpGs displayed significantly higher percentages of partial methylation in nyaope users than in controls. The AG genotype frequency for SNP (118 A&gt;G), was higher in controls than in nyaope users while other genotypes (AA &amp; GG) for SNP rs1799971 and (TT, CT, CC) SNP rs3778150 were broadly similar in both groups. There was no correlation observed between nyaope consumption and the presence of SNP rs1799971 and/or rs3778150 in the study populations.This study provided evidence that methylation may not be associated with the intake of nyaope and that SNPs rs1799971 and rs3778150 did not alter the methylation status of the OPRM1 promoter gene or contribute to nyaope addiction in a black South African male population.