Role Of Single Nucleotide Polymorphisms Research Articles

Can Benzimidazole Resistance Undermine the Philippines’ Success in Controlling and Eliminating Soil-Transmitted Helminth Infections? A Mini-Review

Abstract Soil-transmitted helminth (STH) infections remain a significant global health burden, affecting over 1.5 billion people worldwide. In the Philippines, STH infections continue to be prevalent, despite ongoing control efforts. The Integrated Helminth Control Program (IHCP), whose cornerstone is mass drug administration (MDA) with benzimidazole drugs, has shown some success in reducing STH prevalence in the country. However, the persistence of infection prevalence being above the national and global targets and the potential for benzimidazole resistance have raised concerns about the long-term sustainability of current control strategies. This review examines the development of benzimidazole resistance in STH, focusing on the role of single nucleotide polymorphisms (SNPs) in the β-tubulin isotype that alter the protein’s amino acid constitution, thereby negatively affecting benzimidazole drug binding efficiency. This review discusses the epidemiology of STH infections in the Philippines, the implementation of IHCP and the potential challenges posed by benzimidazole resistance. This review highlights the need for further research to assess the occurrence of benzimidazole resistance in Philippine STH populations and to explore alternative control strategies. Understanding the mechanisms of benzimidazole resistance and developing effective countermeasures is crucial for achieving sustainable STH control and elimination in the Philippines.

Non-alcoholic fatty liver disease: Genetic susceptibility

The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is increasing, particularly in individuals who consume minimal to no alcohol. Currently, NAFLD affects at least 32% of the global population. Although not all but approximately 5-10% cases of NAFLD progress to non-alcoholic steatohepatitis (NASH), a condition arising from lipotoxicity. Patients with NASH may further develop liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, it is important to note that progression from NAFLD to NASH and HCC is not inevitable for all patients. The pathogenesis of HCC in the context of NAFLD and NASH remains poorly understood, however, fat accumulation, often due to obesity or metabolic syndrome, leads to lipotoxicity. In individuals with type 2 diabetes (T2D), elevated insulin levels promote lipolysis in adipose tissue and activate lipid-synthesizing enzymes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), which contribute to lipid accumulation in the liver. Additionally, high glucose levels in T2D can alter gene regulation by activating carbohydrate response-element binding protein (ChREBP) and insulin can increase the activity of sterol regulatory element binding protein (SREBP-1c). These lipogenic transcription factors are known to directly or indirectly activate patatin-like phospholipase domain-containing protein 3 (PNPLA3). Recent research has found elevated levels of angiotensinogen (AGT) and des-angiotensin in both experimental animals and patients with NAFLD. Emerging evidence highlights the significance of genetic factors in the risk of developing NAFLD. Here we explore the association between specific genes and hepatosteatosis, detailing the roles of T2D and obesity in the progression from NAFLD to NASH, and involvement of hepatic stellate cells in liver fibrosis. Additionally, we examine the impact of genes such as PNPLA3, MBOAT7, TM6SF2, GKRP, CCN3, and AGT as well as role of single nucleotide polymorphisms in gene regulation and their contribution to the risk of NAFLD.

The Role of Single Nucleotide Polymorphisms in MicroRNA Genes in Head and Neck Squamous Cell Carcinomas: Susceptibility and Prognosis.

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. MicroRNAs (miRNAs), which belong to the group of important post-transcriptional regulators of human gene expression, seem to be valuable options for consideration as key modifiers of individual cancer risk, and therefore may be helpful in predicting inter-individual differences in cancer risk, response to treatment and prognosis. There have not been many studies focused on the relationship between miRNA variants and HNSCC published in PubMed within the last 15 years. We found and analyzed 30 reviews, meta-analyses and research papers and revealed 14 SNPs which have been reported as significant in the context of HNSCC susceptibility and/or prognosis. These 14 SNPs were located in 13 separate miRNAs. Among them, four were the most frequently studied (miRNA-146, -196, -149 and -499) and have been shown to have the greatest impact on the course of HNSCC. However, the presented results have been conflicting. It must be concluded that, despite the years of studies, there are no conclusive reports demonstrating a significant role of SNPs in miRNAs in the context of the susceptibility to HNSCC or its prognosis.

Pharmacogenetics of acute coronary syndrome: the role of single nucleotide polymorphisms (literature review)

Pharmacogenetics of acute coronary syndrome: the role of single nucleotide polymorphisms (literature review)

Association between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine.

The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. This study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.

Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profile.

The vertical facial profile is a crucial factor for facial harmony with significant implications for both aesthetic satisfaction and orthodontic treatment planning. However, the role of single nucleotide polymorphisms (SNPs) in the development of vertical facial proportions is still poorly understood. This study aimed to investigate the potential impact of some SNPs in genes associated with craniofacial bone development on the establishment of different vertical facial profiles. Vertical facial profiles were assessed by two senior orthodontists through pre-treatment digital lateral cephalograms. The vertical facial profile type was determined by recommended measurement according to the American Board of Orthodontics. Healthy orthodontic patients were divided into the following groups: "Normodivergent" (control group), "Hyperdivergent" and "Hypodivergent". Patients with a history of orthodontic or facial surgical intervention were excluded. Genomic DNA extracted from saliva samples was used for the genotyping of 7 SNPs in RUNX2, BMP2, BMP4 and SMAD6 genes using real-time polymerase chain reactions (PCR). The genotype distribution between groups was evaluated by uni- and multivariate analysis adjusted by age (alpha = 5%). A total of 272 patients were included, 158 (58.1%) were "Normodivergent", 68 (25.0%) were "Hyperdivergent", and 46 (16.9%) were "Hypodivergent". The SNPs rs1200425 (RUNX2) and rs1005464 (BMP2) were associated with a hyperdivergent vertical profile in uni- and multivariate analysis (p-value < 0.05). Synergistic effect was observed when evaluating both SNPs rs1200425- rs1005464 simultaneously (Prevalence Ratio = 4.0; 95% Confidence Interval = 1.2-13.4; p-value = 0.022). In conclusion, this study supports a link between genetic factors and the establishment of vertical facial profiles. SNPs in RUNX2 and BMP2 genes were identified as potential contributors to hyperdivergent facial profiles.

The Landscape of Presence/Absence Variations during the Improvement of Rice

Rice is one of the most important staple crops in the world; therefore, the improvement of rice holds great significance for enhancing agricultural production and addressing food security challenges. Although there have been numerous studies on the role of single-nucleotide polymorphisms (SNPs) in rice improvement with the development of next-generation sequencing technologies, research on the role of presence/absence variations (PAVs) in the improvement of rice is limited. In particular, there is a scarcity of studies exploring the traits and genes that may be affected by PAVs in rice. Here, we extracted PAVs utilizing resequencing data from 148 improved rice varieties distributed in Asia. We detected a total of 33,220 PAVs and found that the number of variations decreased gradually as the length of the PAVs increased. The number of PAVs was the highest on chromosome 1. Furthermore, we identified a 6 Mb hotspot region on chromosome 11 containing 1091 PAVs in which there were 29 genes related to defense responses. By conducting a genome-wide association study (GWAS) using PAV variation data and phenotypic data for five traits (flowering time, plant height, flag leaf length, flag leaf width, and panicle number) across all materials, we identified 186 significantly associated PAVs involving 20 cloned genes. A haplotype analysis and expression analysis of candidate genes revealed that important genes might be affected by PAVs, such as the flowering time gene OsSFL1 and the flag leaf width gene NAL1. Our work investigated the pattern in PAVs and explored important PAV key functional genes associated with agronomic traits. Consequently, these results provide potential and exploitable genetic resources for rice breeding.

Roles of Single Nucleotide Polymorphisms of C3 Gene in Patients with Coronary Artery Disease.

This study aims to investigate the association between nine tag single nucleotide polymorphisms (SNPs) in the C3 gene locus and the risk of coronary artery disease (CAD) as well as lipid levels in the Chinese population, and to further explore the interactions between SNPs and environmental factors that may be associated with CAD risk. A case-control study was conducted to investigate the association between CAD and C3 gene polymorphisms in a hospital setting. The study consisted of 944 CAD patients with a mean age of 55.97 10.182 years and 897 non-CAD controls with a mean age of 55.94 9.162 years. There were 565 males and 288 females in the CAD group and 583 males and 314 females in the control group. TagSNPs in the C3 gene were identified by employing the improved multiplex ligation detection reaction (iMLDR) technique, and multifactor dimensionality reduction (MDR) analysis was utilized to investigate the C3 gene-environment and gene-gene interactions in relation to the risk of CAD. Results of the polymorphism study indicated that the CC genotype of rs7257062 was more frequent in the CAD group compared to the control group (10.9% vs 7.7%), with a statistically significant difference (p = 0.009). Moreover, the TT and CC + CT genotype groups of rs7257062 in the CAD subgroup showed a significant difference in terms of serum triglyceride levels (2.326 1.889 vs 2.059 1.447, p = 0.019). Analysis of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels revealed no significant differences between the TT and CC + CT genotypes. Furthermore, no significant differences in serum lipid levels were observed between genotypes of the other SNPs. Multivariable logistic analysis, controlling for gender, age, body mass index (BMI), triglycerides (TG), TC, HDL-C, LDL-C, ApoA and ApoB, demonstrated that rs7257062 was still an independent risk factor of CAD (OR = 1.499, 95% CI: 1.036-2.168, p = 0.032). MDR analysis revealed that the rs7257062 interacted significantly with environmental factors such as smoking, diabetes, hypertension, BMI, and TG (p 0.05). The rs7257062 variation of the C3 gene could be linked to both lipid balance and the risk of CAD. It is conceivable that the interplay between C3 polymorphisms and environmental elements could account for the etiology of CAD.

Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro.

CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of CALCRL expression in endothelial cells. To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene CALCRL, we applied an integrative approach encompassing statistical, transcriptional (RNA-seq), and epigenetic (ATAC-seq [transposase-accessible chromatin with sequencing], chromatin immunoprecipitation assay-quantitative polymerase chain reaction, and electromobility shift assay) analyses, alongside luciferase reporter assays, and targeted gene and enhancer perturbations (siRNA and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) in human aortic endothelial cells. We demonstrate that the regulatory element harboring rs880890 exhibits high enhancer activity and shows significant allelic bias. The A allele was favored over the G allele, particularly under shear stress conditions, mediated through alterations in the HSF1 (heat shock factor 1) motif and binding. CRISPR deletion of rs880890 enhancer resulted in downregulation of CALCRL expression, whereas HSF1 knockdown resulted in a significant decrease in rs880890-enhancer activity and CALCRL expression. A significant decrease in HSF1 binding to the enhancer region in endothelial cells was observed under disturbed flow compared with unidirectional flow. CALCRL knockdown and variant perturbation experiments indicated the role of CALCRL in mediating eNOS (endothelial nitric oxide synthase), APLN (apelin), angiopoietin, prostaglandins, and EDN1 (endothelin-1) signaling pathways leading to a decrease in cell proliferation, tube formation, and NO production. Overall, our results demonstrate the existence of an endothelial-specific HSF (heat shock factor)-regulated transcriptional enhancer that mediates CALCRL expression. A better understanding of CALCRL gene regulation and the role of single-nucleotide polymorphisms in the modulation of CALCRL expression could provide important steps toward understanding the genetic regulation of shear stress signaling responses.

Association of polymorphic loci of the GSS gene with the risk of acute biliary pancreatitis

Aim. To investigate the role of single nucleotide polymorphisms (SNPs) rs13041792, rs1801310, and rs6088660 in the GSS gene and environmental factors in the development of acute biliary pancreatitis (ABP) and its complications.Materials and methods. The material for the study was blood samples obtained from 84 patients with ABP and 573 healthy individuals. Both groups were comparable in terms of gender and age. To diagnose ABP, we used the clinical guidelines recommended by the working group of the Russian Society of Surgeons. DNA was isolated by phenol / chloroform extraction. Multiplex genotyping of SNPs was performed by the iPLEX assay on the MALDITOF MassARRAY-4 genetic analyzer. Statistical data processing was performed using Statistica 10 and SNPStats software.Results. We found that insufficient consumption of fresh vegetables and fruits increased the probability of ABP in carriers of genotypes G/A-A/A at rs1801310 in GSS (р = 0.02). The analysis revealed the association of the T allele at rs6088660 with the odds for developing acute pancreatitis (р = 0.007) and digestive fistulas (р = 0.02). A high probability of death was associated with rs1801310 (G/A genotype, р = 0.002) and rs6088660 (C/T genotype, р = 0.01) in the GSS gene.Conclusion. SNPs rs6088660 and rs1801310 in the GSS gene can be used to predict the course of ABP.

Role of Single Nucleotide Polymorphisms in BRCA1 and BRCA2 Genes Relative to Previous Studies in Pakistan in the Prognosis of Breast Cancer

Breast cancer is a complex disease characterized by a myriad of genetic alterations. Single nucleotide polymorphisms are particularly relevant due to small allelic variations. BRCA1 and BRCA2 genes are notably associated with inherited breast and ovarian cancers. Alterations in other genes were also identified. Mutations in BRCA1 and BRCA2 tumor suppressor genes play a significant role in development. Studies in the Pakistani population revealed significant differences in gene mutations. In 31 families, 8 had male and 23 had female breast cancer, substantial findings were observed. The analysis encompassed full coding sites of these genetic variations. Among eight families with male BC, changes were detected in 2 BRCA1 and 4 BRCA2 genes. Additionally, eight alterations were noted in 23 females from site-specific families, with 4 in BRCA1 and 4 in BRCA2. These findings underscore the importance of genetic variations, especially in the BRCA1 and BRCA2 genes, in the context of breast cancer susceptibility within diverse populations.

Assessing the association of ESR1 polymorphisms with male infertility in Vietnamese population

Male infertility is a prevalent global concern, impacting an estimated 7% of the male population. Many single nucleotide polymorphisms (SNPs) linked to idiopathic male infertility have been discovered since the 1990s, including two intronic SNPs of the estrogen receptor α gene (ESR1), namely rs9340799 and rs2234693. However, the associations of the two SNPs with male infertility have yielded inconsistent results across different populations. In this study, we aimed to assess the association of ESR1 rs9340799 and ESR1 rs2234693 with male infertility in a cohort of Vietnamese individuals consisting of 154 fertile men and 146 infertile men. Genotyping ESR1 rs9340799 and ESR1 rs2234693 for 300 samples was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP). The frequencies of genotypes and alleles were analyzed using bioinformatic tools. The genotype distributions of ESR1 rs9340799 and ESR1 rs2234693 followed Hardy-Weinberg equilibrium, but no association of the two SNPs with male infertility was established (p &gt; 0.05) in the additive, dominant, recessive, and allele models. Notably, the haplotype analysis revealed a strong association between the haplotype GT and a decreased risk of male infertility (OR = 0.226; 95% CI = 0.106 - 0.484; p &lt; 0.001). The findings provide additional knowledge about the roles of single nucleotide polymorphisms in male infertility in the Vietnamese population.

Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort.

Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism-related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort. A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression. Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression [odds ratio 2.3 (95% confidence interval 1.06-4.9)] and higher risk of suffering a CVE [hazard ratio 2.16 (95% confidence interval 1.13-4.12)] compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample. The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.

Potential of GJA8 gene variants in predicting age-related cataract: A comparison of supervised machine learning methods.

Cataracts are the problems associated with the crystallins proteins of the eye lens. Any perturbation in the conformity of these proteins results in a cataract. Age-related cataract is the most common type among all cataracts as it accounts for almost 80% of cases of senile blindness worldwide. This research study was performed to predict the role of single nucleotide polymorphisms (SNPs) of the GJA8 gene with age-related cataracts in 718 subjects (400 age-related cataract patients and 318 healthy individuals). A comparison of supervised machine learning classification algorithm including logistic regression (LR), random forest (RF) and Artificial Neural Network (ANN) were presented to predict the age-related cataracts. The results indicated that LR is the best for predicting age-related cataracts. This successfully developed model after accounting different genetic and demographic factors to predict cataracts will help in effective disease management and decision-making medical practitioner and experts.

COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics.

An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age. Therefore, the aim of this study was to evaluate the role of single nucleotide polymorphisms in these pathways, clarifying their impact in affecting COVID-19-related clinical features. Genetic polymorphisms were evaluated through real-time PCR. We prospectively enrolled 160 individuals: 139 patients were positive for SARS-CoV-2 detection. We detected different genetic variants able to affect the symptoms and oxygenation. Furthermore, two sub-analyses were performed considering gender and age, showing a different impact of polymorphisms according to these characteristics. This is the first study highlighting a possible contribution of genetic variants of these pathways in affecting COVID-19 clinical features. This may be relevant in order to clarify the COVID-19 etiopathogenesis and to understand the possible genetic contribution for further SARS infections.

The role of single nucleotide polymorphisms within genes for oxytocin and vasopressin receptors in the presentation and severity of autistic traits

IntroductionAutism spectrum disorder is a heterogeneous group of disorders that affects virtually every population, regardless of their ethnic or socioeconomic origin. The pathogenesis of ASD is probably multifactorial, based on interactions between genetic and environmental factors. Their key elements are disorders in the field of social communication, establishing and maintaining relationships and the so-called stereotypical and repetitive patterns of interests and activities. However, of the above- mentioned symptoms, the most important are communication disorders, which are the basis for many of the functional difficulties observed in these patients.ObjectivesThe aim of the presented study was to analyze the clinical picture of social cognition deficits in males with autism spectrum disorders, and to link its elements with the frequency of alleles of selected polymorphisms within the OXTR and AVPR1A genes.MethodsThe study included 132 people, 77.5% of whom were male (n = 100). 113 participants (85.6%) were diagnosed with autism spectrum disorders confirmed by the ADOS-2 test conducted by a certified diagnostician. In this group, men constituted 76.1% of the population (n = 77). The remaining 28 people did not have a diagnosis of autism spectrum disorders, and in the ADOS-2 study they obtained the result below the cut-off level. The mean age in the whole group was 14.4 years (95% CI: 13.92-14.93).ResultsA higher frequency of the rs53576 A allele and the rs10877969 C allele could be observed than expected on the basis of the European / world population. In the case of the rs7294536 and rs2254298 polymorphisms, no differences in the distribution of alleles in relation to the expected values were observed. In the network analysis reference allele (T) of SNPs rs10877969 was linked to the higher outcome of the “social affect” domain of ADOS-2 and through it influenced ADOS-2 outcome. All other SNPs did not significantly affect neither domain of ADOS-2. Reference allele (A) of rs53576 was linked with higher odds ratio of clinical diagnosis of ASD in logistic regression. Similarly the rs10877969 polymorphism within the AVPR1a gene significantly shaped the risk of autism spectrum disorders, while in the combined analysis with rs7294536 within the haplotype, the observed effect was significantly stronger.ConclusionsThe studied polymorphisms may constitute an element of larger haplotypes which, depending on the number of mutated alleles, may determine the severity of autism spectrum traits, from the neurotypical population, through people with a broad autism phenotype, to people diagnosed with ASD. Further research is required on the potential clinical application of genotype analysis of the studied polymorphisms and on the exact mechanism of their impact on the risk of ASD and the development of social cognition disorders.Disclosure of InterestNone Declared

The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls

The initiation of puberty is a crucial timepoint of development, with its disruptions being associated with multiple physical and psychological complications. Idiopathic Central Precocious Puberty (iCPP) has been correlated with Single-Nucleotide Polymorphisms (SNPs) of certain genes that are implicated in various steps of the process of pubertal onset. The aim of this review was to gather current knowledge on SNPs of genes associated with iCPP. We searched articles published on the PubMed, EMBASE and Google Scholar platforms and gathered current literature. KISS1, KISS1R, PLCB1, PRKCA, ITPR1, MKRN3, HPG axis genes, NPVF/NPFFR1, DLK1, KCNK9Q, LIN28B, PROK2R, IGF-1, IGF2, IGF-1R, IGF-2R, IGFBP-3, insulin, IRS-1, LEP/LEPR, PPARγ2, TAC3, TACR3, Estrogen receptors, CYP3A4 and CYP19A1 were studied for implication in the development of precocious puberty. SNPs discovered in genes KISS1, KISS1R, PLCB1, MKRN3, NPVF, LIN28B, PROK2R, IRS-1 TAC3, and CYP3A4 were significantly correlated with CPP, triggering or protecting from CPP. Haplotype (TTTA)13 in CYP19A1 was a significant contributor to CPP. Further investigation of the mechanisms implicated in the pathogenesis of CPP is required to broaden the understanding of these genes' roles in CPP and possibly initiate targeted therapies.

Challenges and opportunities for omics-based precision medicine in chronic low back pain.

Chronic low back pain (cLBP) is a common health condition worldwide and a leading cause of disability with an estimated lifetime prevalence of 80-90% in industrialized countries. However, we have had limited success in treating cLBP likely due to its non-specific heterogeneous nature that goes beyond detectable anatomical changes. We propose that omics technologies as precision medicine tools are well suited to provide insight into its pathophysiology and provide diagnostic markers and therapeutic targets. Therefore, in this review, we explore the current state of omics technologies in the diagnosis and classification of cLBP. We identify factors that may serve as markers to differentiate between acute and chronic cases of low back pain (LBP). Finally, we also discuss some challenges that must be overcome to successfully apply precision medicine to the diagnosis and treatment of cLBP. A literature search for the current applications of omics technologies to chronic low back pain was performed using the following search terms- "back pain," "low back pain," "proteomics," "transcriptomics", "epigenomics," "genomics," "omics." We reviewed molecular markers identified from 35 studies which hold promise in providing information regarding molecular insights into cLBP. GWAS studies have found evidence for the role of single nucleotide polymorphisms (SNPs) associated with pain pathways in individuals with cLBP. Epigenomic modifications in patients with cLBP have been found to be enriched among genes involved in immune signaling and inflammation. Transcriptomics profiles of patients with cLBP show multiple lines of evidence for the role of inflammation in cLBP. The glycomics profiles of patients with cLBP are similar to those of patients with inflammatory conditions. Proteomics and microbiomics show promise but have limited studies currently. Omics technologies have identified associations between inflammatory and pain pathways in the pathophysiology of cLBP. However, in order to integrate information across the range of studies, it is important for the field to identify and adopt standardized definitions of cLBP and control patients. Additionally, most papers have applied a single omics method to a sampling of cLBP patients which have yielded limited insight into the pathophysiology of cLBP. Therefore, we recommend a multi-omics approach applied to large global consortia for advancing subphenotyping and better management of cLBP, via improved identification of diagnostic markers and therapeutic targets.