Several Single Nucleotide Polymorphisms Research Articles

GPX2 Gene Affects Feed Efficiency of Pigs by Inhibiting Fat Deposition and Promoting Muscle Development.

GPX2 has been recognized as a potential candidate gene for feed efficiency in pigs. This article aimed to elucidate polymorphism of GPX2 associated with feed efficiency and its related molecular mechanism. In this study, seven single nucleotide polymorphisms (SNP) of GPX2 were found among 383 Duroc pigs. In addition, seven SNPs and ALGA0043483 (PorcineSNP60 BeadChip data in 600 Duroc pigs), which are near the GPX2 gene, were identified in one haplotypes block. Furthermore, associated studies showed that the genotype of GPX2 has significant association with weaning weight and 100 kg BF in Duroc pigs. In addition, the AG had no effect when the backfat became thinner, and the FCR and RFI traits had a tendency to decrease in the G3 + TT combination genotype, accompanied by an increase of GPX2 expression in backfat and muscle tissues. At the cellular level, the adipocyte proliferation and ability of adipogenic differentiation were reduced, and the lipid degradation increased in 3T3-L1 when there was overexpression of GPX2. In contrast, overexpression of the GPX2 gene can promote the muscle cell proliferation and myogenic differentiation in C2C12 cells. In other words, GPX2 has the effect of reducing fat deposition and promoting muscle development, and it is a candidate gene for backfat and feed efficiency.

Genome-Wide Association Study (GWAS) and genome prediction of seedling salt tolerance in bread wheat (Triticum aestivum L.)

BackgroundSalinity tolerance in wheat is imperative for improving crop genetic capacity in response to the expanding phenomenon of soil salinization. However, little is known about the genetic foundation underlying salinity tolerance at the seedling growth stage of wheat. Herein, a GWAS analysis was carried out by the random-SNP-effect mixed linear model (mrMLM) multi-locus model to uncover candidate genes responsible for salt tolerance at the seedling stage in 298 Iranian bread wheat accessions, including 208 landraces and 90 cultivars.ResultsA total of 29 functional marker-trait associations (MTAs) were detected under salinity, 100 mM NaCl (sodium chloride). Of these, seven single nucleotide polymorphisms (SNPs) including rs54146, rs257, rs37983, rs18682, rs55629, rs15183, and rs63185 with R2 ≥ 10% were found to be linked with relative water content, root fresh weight, root dry weight, root volume, shoot high, proline, and shoot potassium (K+), respectively. Further, a total of 27 candidate genes were functionally annotated to be involved in response to the saline environment. Most of these genes have key roles in photosynthesis, response to abscisic acid, cell redox homeostasis, sucrose and carbohydrate metabolism, ubiquitination, transmembrane transport, chromatin silencing, and some genes harbored unknown functions that all together may respond to salinity as a complex network. For genomic prediction (GP), the genomic best linear unbiased prediction (GBLUP) model reflected genetic effects better than both bayesian ridge regression (BRR) and ridge regression-best linear unbiased prediction (RRBLUP), suggesting GBLUP as a favorable tool for wheat genomic selection.ConclusionThe SNPs and candidate genes identified in the current work can be used potentially for developing salt-tolerant varieties at the seedling growth stage by marker-assisted selection.

Association between single-nucleotide polymorphisms in ARID4A gene and sperm quality of Chinese water buffalo

ARID4A (AT-rich interaction domain 4A) is closely related to animal sperm quality traits. In the present study, the association between ARID4A gene polymorphisms of Chinese water buffalo (Bubalus bubalis) with sperm quality traits was examined, including ejaculate volume, sperm concentration, post-thaw sperm motility, and sperm abnormality of buffalo semen. Seven single-nucleotide polymorphisms (SNPs) of ARID4A gene were detected in 156 Chinese water buffaloes by Sanger sequencing and identifying overlap peaks. Among the SNPs, six were associated with at least one sperm quality trait. In brief, g.21192G>C, g.21285C>G, and g.21364A>G could be used as potential markers for selecting semen with low sperm abnormality, high ejaculate volume, sperm concentration, and sperm motility. Furthermore, 10 haplotypes (H1: -CTCGG, H2: GTGGCA, H3: GCGGCA, H4: GCTGCA, H5: GCTCGA, H6: GTGGGG, H7: GCTCCG, H8: -CGGGA, H9: GCGGCG, and H10: GTTGCA) were formed by the six SNPs through linkage disequilibrium analysis, and then 14 different combined haplotypes were collected. Correlation analysis showed that the combined H1H2 haplotype had the highest genotype frequency. Notably, the combined H1H2 haplotype had low sperm concentration, low sperm motility, and high sperm abnormality. The combined H2H3 haplotype could be used as a potential molecular marker for selecting semen with high sperm motility. In general, we illustrated a significant correlation between SNPs in ARID4A and sperm quality traits of Chinese water buffalo, which may be useful in the marker-assisted selection of buffalo breeding. This study was the first to analyze the genetic polymorphisms of ARID4A and association with sperm qualities of Chinese buffalo.

Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms

Abdominal aortic aneurysms (AAA) is a multifactorial complex disease with life-threatening consequences. While Genome-wide association studies (GWAS) have revealed several single nucleotide polymorphisms (SNPs) located in the genome of individuals with AAA, the link between SNPs with the associated pathological signals, the influence of risk factors on their distribution and their combined analysis is not fully understood. We integrated 86 AAA SNPs from GWAS and clinical cohorts from the literature to determine their phenotypical vulnerabilities and association with AAA risk factors. The SNPs were annotated using snpXplorer AnnotateMe tool to identify their chromosomal position, minor allele frequency, CADD (Combined Annotation Dependent Depletion), annotation-based pathogenicity score, variant consequence, and their associated gene. Gene enrichment analysis was performed using Gene Ontology and clustered using REVIGO. The plug-in GeneMANIA in Cytoscape was applied to identify network integration with associated genes and functions. 15 SNPs affecting 20 genes with a CADD score above ten were identified. AAA SNPs were predominantly located on chromosome 3 and 9. Stop-gained rs5516 SNP obtained high frequency in AAA and associated with proinflammatory and vascular remodeling phenotypes. SNPs presence positively correlated with hypertension, dyslipidemia and smoking history. GO showed that AAA SNPs and their associated genes could regulate lipid metabolism, extracellular matrix organization, smooth muscle cell proliferation, and oxidative stress, suggesting that part of these AAA traits could stem from genetic abnormalities. We show a library of inborn SNPs and associated genes that manifest in AAA. We uncover their pathological signaling trajectories that likely fuel AAA development.

Single Nucleotide Polymorphisms of ADH1B, ADH1C and ALDH2 Genes in 235 People Living in Thai Nguyen Province of Vietnam.

ADH1B, ADH1C and ALDH2 genes are mainly responsible for alcohol metabolism in the body. Several single nucleotide polymorphisms (SNPs) of these genes have been reported to be associated with alcohol dependence and are considered risk factors for various human diseases. This study aims to identify the prevalence of three SNPs of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) in 235 unrelated individuals living in Thai Nguyen province, the northeast region of Vietnam. The target genotypes were identified by using PCR direct sequencing, and their frequencies were compared to previous reports. Our data showed that allele frequencies of ADH1B*2, ADH1C*2 and ALDH2*2 were 68.8%, 8.3% and 20.4%, respectively. The ADH1B*2 and ADH1C*2 frequencies were similar to those of the Kinh ethnic individuals living in the south region of Vietnam, while the ALDH2*2 frequency was higher. Compared to data from other countries, ADH1B*2 frequency is similar to the Philippines (60.5%) and Mongolia (62.9%) but significantly different from the other populations. The ADH1C*2 frequency is not so different compared to Japanese (5.7%) and Chinese (7.1%) but is quite different in other populations. ALDH2*2 frequency was lower than Japanese (29.3%), Indonesian (30%) and higher than other countries. Regarding the risk of alcoholism, the percentage of Vietnamese people in this study with genotypes related to alcohol dependence is 8.1%. In contrast, the carrier has genotypes protecting against alcoholism with high frequency, 91.9%. Among them, the individuals can cause high acetaldehyde accumulation accounting for 33.2%. This study helps to understand the genetic polymorphisms of alcohol metabolism genes in the community living in Thai Nguyen province, northeast of Vietnam, and provides valuable scientific data relating to alcohol consumption behavior as well as public health protection.

Causal relationship between particulate matter 2.5 and hypothyroidism: A two-sample Mendelian randomization study.

Epidemiological surveys have found that particulate matter 2.5 (PM2.5) plays an important role in hypothyroidism. However, due to the methodological limitations of traditional observational studies, it is difficult to make causal inferences. In the present study, we assessed the causal association between PM2.5 concentrations and risk of hypothyroidism using two-sample Mendelian randomization (TSMR). We performed TSMR by using aggregated data from genome-wide association studies (GWAS) on the IEU Open GWAS database. We identified seven single nucleotide polymorphisms (SNPs) associated with PM2.5 concentrations as instrumental variables (IVs). We used inverse-variance weighting (IVW) as the main analytical method, and we selected MR-Egger, weighted median, simple model, and weighted model methods for quality control. MR analysis showed that PM2.5 has a positive effect on the risk of hypothyroidism: An increase of 1 standard deviation (SD) in PM2.5 concentrations increases the risk of hypothyroidism by ~10.0% (odds ratio 1.10, 95% confidence interval 1.06-1.13, P = 2.93E-08, by IVW analysis); there was no heterogeneity or pleiotropy in the results. In conclusion, increased PM2.5 concentrations are associated with an increased risk of hypothyroidism. This study provides evidence of a causal relationship between PM2.5 and the risk of hypothyroidism, so air pollution control may have important implications for the prevention of hypothyroidism.

BDNF rs10501087, rs1491850 and rs11030094 polymorphisms associated with delayed progression in early-stage Parkinson's disease.

Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene BDNF have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other BDNF SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (n = 217) were genotyped for the BDNF rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6-223.1, p = 0.002) and 7.6 (1.9-29.8, p = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3-8.4, p = 0.04) and 2.8 (1.3-6.4, p = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1-5.6, p = 0.03) and 2.0 (1.3-6.4, p = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many BDNF SNPs is warranted.

Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.

Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A. A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe. Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n=15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n=23) or modified FOLFIRINOX for pancreatic cancer (n=40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p=0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n=66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n=47). Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.

Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases.

The endocannabinoid (eCB) system is an important neuromodulatory system with its extensive network of receptors throughout the human body that has complex actions in the nervous system, immune system, and all of the body's other organs. Fatty acid amide hydrolase (FAAH) is an important membrane-bound homodimeric degrading enzyme that controls the biological activity of N-arachidonoylethanolamide (AEA) in the eCB system and other relevant bioactive lipids. It has been shown that several single nucleotide polymorphisms (SNPs) of FAAH are associated with various phenotypes and diseases including cardiovascular, endocrine, drug abuse, and neuropsychiatric disorders. A common functional and most studied polymorphism of this gene is C385A (rs324420), which results in the replacement of a conserved proline to threonine in the FAAH enzyme structure, leads to a reduction of the activity and expression of FAAH, compromises the inactivation of AEA and causes higher synaptic concentrations of AEA that can be associated with several various phenotypes. The focus of this review is on evidence-based studies on the associations of the FAAH C385A polymorphism and the various diseases or traits. Although there was variability in the results of these reports, the overall consensus is that the FAAH C385A genotype can affect susceptibility to some multifactorial disorders and can be considered a potential therapeutic target.

MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population

BackgroundsMIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population.MethodsA total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model.ResultsAccording to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p < 0.001) and male populations (OR = 0.35, p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50, p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001).ConclusionThe study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role of MIR31HG in the pathogenesis of SONFH.

Genetic associations with lymphomas in Polish patients: A pooled-DNA genome-wide association analysis.

Several single nucleotide polymorphisms (SNPs) associated with susceptibility to Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have been identified. The aim of this study was to identify susceptibility loci for HL and DLBCL in Polish patients. Altogether, DLBCL (n=218 and HL patients (n=224) and healthy individuals (n=1181) were recruited. Lymphoma diagnosis was based on standard criteria. Genome-wide association study (GWAS) was performed using pooled-DNA samples on llumina Infinium Omni2.5 Exome-8 v1.3, and selected loci were replicated by TaqMan SNP genotyping of individuals. GWAS detected thirteen and seven SNPs associated with DLBCL and HL, respectively. In the replication study, six and seven SNPs reached significance after correction for multiple testing in the DLBCL and HL cohorts, respectively. One and four SNPs associated with DLBCL and HL, respectively, were localized within, and two SNPs-near the major histocompatibility complex (MHC) region. In conclusion, the majority of loci associated with HL and DLBCL aetiology in previous studies have potential roles in immune function. Our pooled-DNA GWAS enabled the identification of several susceptibility loci for DLBCL and HL in the Polish population; some of them were mapped within or adjacent to the MHC, and other associated SNPs were located outside the MHC.

Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease.

ResumoFundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas.Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC).Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante.Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019).Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Identification of missense SNP-mediated mutations in the regulatory sites of aldose reductase (ALR2) responsible for treatment failure in diabetic complications.

Scientific pieces of evidence indicate that the polymorphism in the ALR2 regulatory gene favors the susceptibility to diabetic complications (DCs). Previous studies have uncovered several single nucleotide polymorphisms (SNPs) in the ALR2 regulatory sites that negatively modulate the activity of this enzyme and eventually increase the risks of DCs. In view of this, the current study aimed at investigating whether the mutation as a resultant of missense SNPs in the regulatory site of ALR2 enzyme can also hamper the interactions of ALR2 inhibitors with the key amino acid residues in the ALR2 binding site. Around 202 SNPs in the ALR2 gene were reported in the dbSNP database. Out of these, eighteen SNPs that are responsible for point mutations in the regulatory sites of ALR2 enzyme were identified and considered for the study. Identified SNPs were then categorized as stabilizing or destabilizing using various in silico tools and webservers. The resulting mutational constructs of ALR2 were further probed for their influence on the binding affinities and binding modes with well-known ALR2 inhibitors using structure-based analyses. This study identified three destabilizing SNPs, i.e., rs779176563 (C298S), rs1392886142 (G16A), and rs1407261115 (A245T), that lead to the compromised response to most of the ALR2 inhibitors which are in clinical trials. On the other hand, treatment with these ALR2 inhibitors may benefit the population which carries missense SNPs rs748119899, rs1402962430, and rs1467939858 that code for W219S, Q183V, and S214A, respectively. Overall findings of the study suggest that one SNP in the inhibitor site and two SNPs in the co-factor site of ALR2 may be responsible for the low efficacy and unsuccessful journey of ALR2 inhibitors in the clinical trials.

Association of IKZF1 and CDKN2A gene polymorphisms with childhood acute lymphoblastic leukemia: a high-resolution melting analysis

BackgroundAcute lymphoblastic leukemia is the most prevailing pediatric hematologic malignancy, and various factors such as environmental exposures and genetic variation affect ALL susceptibility and patients outcome. According to genome-wide association studies, several single nucleotide polymorphisms (SNPs) in IKZF1 (rs4132601) and CDKN2A (rs3731249 and rs3731217) genes are associated with ALL susceptibility. Hereupon, this study aimed to discover the association between these SNPs and the risk of childhood ALL among a sample of the Iranian population.MethodsA total of fifty children with ALL were included in this case–control study, along with an additional fifty healthy children, matched for age and gender. High-resolution melting (HRM) analysis was employed to genotyping rs4132601, rs3731249, and rs3731217.ResultsIn the patient group, the CT genotype and T allele frequency of rs3731249 were significantly greater than controls (p = 0.01 and p = 0.005, respectively). Moreover, the positive association of CT and dominant model (CT + TT) genotypes and T allele at rs3731249 with the risk of ALL was confirmed (OR = 9.56, OR = 10.76 and OR = 11.00, respectively). There was no significant relation between rs4132601 (IKZF1), rs3731217 (CDKN2A), and childhood ALL.ConclusionThe present study indicates that CT genotype and T allele at rs3731249 (CDKN2A) can significantly increase the risk of ALL among children.

Genetic variation in ADAMTS13 are related to vWF levels, atrial fibrillation and cerebral ischemic events

Background and Aims : ADAMTS13 is a metalloprotease cleaving ultra-large von Willebrand Factor (vWF) multimers into less active fragments. ADAMTS13 and vWF have both been related to cardiovascular disease (CVD). Several single nucleotide polymorphisms (SNPs) in the ADAMTS13 gene have been described. We aimed to investigate the influence of ADAMTS13 genetic variants on levels of ADAMTS13 and vWF, the SNPs’ frequencies in subgroups of CVD and further any associations with clinical outcome after 2 years follow-up.

Single Nucleotide Polymorphism rs6445975 in the PXK Gene Is Correlated with Susceptibility and Clinical Characteristics of Systemic Lupus Erythematosus.

Background:Recently, genome-wide association studies (GWAS) have discovered several single nucleotide polymorphisms (SNPs) and loci associated with the risk of systemic lupus erythematosus (SLE). rs6445975 (T>G; intronic variant) polymorphism in the PXK gene is one of these loci. However, there was an inconsistency between the results of replicative studies on European and Asia ancestry. This study aimed to assess the possible association between rs6445975 polymorphism with SLE risk in the Iranian population.Methods:Genotype and allele distribution of rs6445975 polymorphism were investigated in 110 patients with SLE and 115 healthy controls in Isfahan University of Medical Sciences, Isfahan, Iran in 2019 via real-time PCR high resolution melting method (HRM).Results:GG and TG genotypes, but not TT genotype, were associated with increased risk of SLE (GG vs TT; OR= 7.538; 95%CI [3.47, 17.066] and TG vs TT; OR=2.21; 95%CI [1.06, 4.72]). Inheritance analysis revealed that TG + GG was correlated with the increased risk of SLE disease in the dominant model (OR=3.928; 95%CI [2.056, 7.74]). Moreover, subjects with the G allele were more frequently affected with SLE than individuals with the T allele (OR= 3.55; 95%CI [2.37, 5.36]). The G allele in patients was correlated with serum concentration of CRP, ESR, anti-dsDNA antibody, C3, and C4 and presentation of some clinical manifestations such as kidney involvements and skin lesions (P<0.05).Conclusion:Our findings suggest a substantial association between rs6445975 polymorphism in the PXK gene with susceptibility and clinical characteristics of SLE in the Iranian population.

The Correlation Between Toll-Like Receptor-5 Gene Polymorphism with Serum Level of Toll–Like Receptor-5 and Interleukin-6 and Interleukin-12 Response to Toxoplasma Gondii in Pregnant Women

Background: Toxoplasma gondii is an obligate intracellular parasite that can cause variable clinical symptoms or can even be asymptomatic in immunocompetent individuals. The parasite is known to cause congenital diseases, ocular, and miscarriage in pregnant women. Primary infections are dangerous in pregnant women, that occurring usually asymptomatically, especially in the first trimester. Different rates of pregnant women are infected with Toxoplasma gondii in different countries. Primary infections in pregnant women result in transmission of Toxoplasma. gondii through the placenta to the fetus and then in congenital infections, and it is not the only reason for miscarriage, the activity of Toll -like receptors in defense against Toxoplasma gondii infections was observed such as Toll-like receptor5 molecule, and some cytokines (such as IL-6, and IL-12 ), maybe lead to abortion. Several single-nucleotide polymorphisms (SNPs) residing in genes encoding these receptors were reported as significant genetic modifications of Toll- like receptors and correlated with miscarriage. Objectives : Study the correlation of TLR-5 gene polymorphism in pregnant women infected with toxoplasmosis, and study association of TLR-5 polymorphisms with the serum level of TLR-5 and cytokines (IL-6, IL-12) in pregnant women infected with toxoplasmosis. Methods: The present Case-control study was conducted on 100 women, of which fifty pregnant women seropositive (IgG, IgM) for Toxoplasma gondii (Group1), fifty pregnant women seronegative (IgG, IgM) for Toxoplasma gondii (Group2), as a control group, collected in the period from January 2021 to December 2021.

The Associations between Metalloestrogens, GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer.

Background: The incidence of endometrial cancer (EC) is still rising. Numerous risk factors including patient characteristics and molecular instability have been identified for EC. The presence of specific molecular markers allows specific diagnostic and prognostic approaches. Several single nucleotide polymorphisms (SNPs) have been identified to influence endometrial cancer risk. Metalloestrogens are metal ions which can mimic estrogen activity; however, their role in uterine pathologies remains unknown. This study aimed to investigate total blood trace elements levels and evaluate the distribution of selected genotypes in GSTP1 and SLC11A2 genes. Methods: This retrospective case-control analysis was carried out in peripheral blood samples of 110 women with endometrial cancer (EC; n = 21), uterine fibroma (n = 25), endometrial polyp (n = 48), and normal endometrium (n = 16). Analysis included measurement of metals and phosphor in serum, and of genetic polymorphisms in GST (rs1695) and SLC11A2 (rs224589) in DNA from white blood cells. Serum trace elements were measured using ICP-OES spectrometry. SNPs were identified using Taq Man real-time PCR genotyping assays. Results: The study confirmed higher age (OR 2.19, 95% CI 1.69–2.24), post-menopausal status (OR 1.89, 95% CI 1.36–1.94), and diabetes type 2 (OR 1.54; 95% CI 0.97–1.72) as independent risk factors for EC. We also found a high level of Cd (OR 1.49; 95% CI 1.31–1.63) and a low level of Co (OR 0.76; 95% CI 0.53–0.59) to be independent risk factors of EC. None of the tested polymorphisms of GSTP1 and SLC11A2 were associated with EC risk. However, high Cd (OR 1.21, 95% CI 1.15–1.29) and Ni (OR 1.07, 95% CI 1.05–1.18) serum levels were significantly associated with a SLC1A2 TG genotype, and high Cd levels with GSTP1 (OR 1.05, 95% CI 1.01–1.13).

Genetic Elements at the Alpha-Synuclein Locus.

Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson’s disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that SNCA is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus. Recent evidence has shown that the risk associated with the top GWAS-identified variant within this locus is independent of SNCA expression, calling into question the validity of assigning function to the nearest gene, SNCA. In this review, we examine additional genes and risk variants present at the SNCA locus and how they may contribute to Parkinson’s disease. Using the SNCA locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.

Warfarin Therapy and Pharmacogenetics

The aim of this work was to review several studies investigating the effects of genetic polymorphisms on warfarin dosing in regional and Iraqi studies and to report any consistent pattern of relevant findings. Despite the growing use of the recently introduced direct oral anticoagulants, warfarin is still the mainstay agent for oral anticoagulation because of its cost-effectiveness. However, a difficulty to establish a stable warfarin dose is frequently encountered. In addition to the warfarin narrow window of efficacy and safety, the main contributor to the challenging dosing is the wide range of variability in warfarin pharmacokinetics and pharmacodynamics among different patients as well as within the single patient context. A link between nonappropriateness of warfarin doses and dramatically increased risk of thromboembolic and hemorrhagic events has been well documented. Several single nucleotide polymorphisms (SNPs) in the genes implicated in warfarin pharmacokinetic and pharmacodynamic processes have been highlighted as possible contributors to warfarin dosing instability. Vitamin K epoxide reductase complex 1 gene SNPs have consistently been found to be the predominant genetic factor contributing the dosing variations. The SNP rs9923231 was significantly associated with the greatest predicting capability of warfarin dosage. However, a range of about 30%–50% of the variances in warfarin dosing was explained by the combined contribution effect of several genetic and nongenetic (clinical) factors in the regional and Iraqi studies.