Gene Polymorphisms Research Articles

Relationships between growth characteristics and GDF9 gene polymorphisms in Awassi sheep

Relationships between growth characteristics and GDF9 gene polymorphisms in Awassi sheep

Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder.

This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes (CYP2R1, CYP27B1, GC, and VDR) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041C/rs4588G) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms' roles.

Circulating VEGF levels and genetic polymorphisms in Behçet’s disease: a meta-analysis

Circulating VEGF levels and genetic polymorphisms in Behçet’s disease: a meta-analysis

Association and interaction analysis of NLRP3 gene polymorphisms with hypertension risk: a case-control study in China.

The NLRP3 inflammasome, a pivotal mechanism regulating inflammatory responses and featuring the pyrin domain containing 3 (NLRP3) within the NOD-like receptor family, is widely recognized as a central pathogenic factor in cardiovascular diseases. The present study endeavors to delve into the correlation and potential interplay between the rs10754558 polymorphism of NLRP3 and the predisposition to hypertension among the Chinese adult population. All the participants who came from a community in Bengbu, China were investigated by being interviewed with a questionnaire. Overall, 354 paired case-control participants were analyzed. Genomic DNA was extracted from 5ml venous blood using the Tiangen DNA extraction kit. The rs10754558 polymorphism of the NLRP3 gene was genotyped by TaqMan allelic discrimination real-time PCR.The association between the rs10754558 polymorphism and hypertension risk was investigated by a logistic regression analysis. Furthermore, an additive interaction analysis was conducted using related indicators, including the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). Participants carrying the GG genotype were more likely to develop hypertension than participants carrying the CC genotype (adjusted odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.33-3.52). A significant additive interaction between the NLRP3 polymorphism and obesity status concerning the risk of hypertension was observed, as estimated by all indicators: RERI (1.12, 95% CI: 0.70-1.5), AP (0.34, 95% CI: 0.14-0.53), and SI (1.92, 95% CI: 1.03-3.59). The values of RERI (1.74, 95% CI: 0.37-3.11), AP (0.46, 95% CI: 0.21-0.70), and SI (2.62, 95% CI: 1.18-5.83) showed that a significant interaction between the rs10754558 polymorphism and a family history of hypertension. Our findings indicate a significant association between the NLRP3 rs10754558 polymorphism and the risk of hypertension in Chinese adults. Moreover, a notable additive interaction emerges between NLRP3 polymorphisms and obesity status, further amplifying the risk of hypertension.

Population pharmacokinetic study of the effect of polymorphisms in the ABCB1 and CES1 genes on the pharmacokinetics of dabigatran

PurposeThe impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantitatively assess the effects of genetic polymorphisms on dabigatran esters in healthy Chinese subjects employed a population pharmacokinetic (PopPK) approach.MethodsIn total, 1,926 pharmacokinetic (PK) samples from 123 healthy individuals who were given 150 mg of dabigatran orally during a fasting state or postprandially were analyzed using the PopPK model. A two-compartment model with first-order absorption was found to adequately describe the PK data.ResultsThe results showed that covariates food intake and ABCB1 SNP rs4148738 were shown to have statistically significant impacts. Specifically, in postprandial administration increased lag time (ALAG) and clearance (CL) by 2.65% and 0.51%, respectively, and decreased absorption rate constant (KA) by 0.24%. Additionally, in subjects with CT genotype ABCB1 (rs4148738), the central ventricular volume of distribution (V2) was increased by 0.38%.ConclusionIn summary, the PopPK model developed in this study was robust and effectively characterized the pharmacokinetics of dabigatran in healthy Chinese adults, demonstrating that both food and ABCB1 genetic variation significantly influence the absorption and plasma concentration levels of dabigatran.

Interactive effects of ARRB2 and CHRNA5 genetic polymorphisms on cognitive function in Chinese male methamphetamine use disorder patients.

Both β-arrestin2 and nicotinic acetylcholine receptor (nAChR) have been implicated in cognitive processes, particularly in relation to psychiatric disorders, including addiction. Previous studies have suggested that nAChR may be regulated by β-arrestin2. However, no study has investigated the interaction of β-arrestin2 and nAChR on cognition. We aimed to examine the main and interactive effects of their respective encoding genes, ARRB2 and CHRNA5, on cognitive function in MUD patients. We recruited 559 patients with methamphetamine use disorder (MUD) and 459 healthy controls, assessed their cognitive functioning using the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and genotyped ARRB2 rs1045280 and CHRNA5 rs3829787 polymorphisms in MUD patients. Compared to healthy controls, MUD patients scored significantly lower on all RBANS indexes. Neither ARRB2 rs1045280 nor CHRNA5 rs3829787 had main effects on cognitive function in MUD patients, but there were significant interactive effects between the two single nucleotide polymorphisms (SNPs) on multiple RBANS indexes, including immediate memory, visuospatial/constructional, delayed memory, and total score. In detail, among carriers of CHRNA5 rs3829787 T allele, ARRB2 rs1045280 TT carriers had higher RBANS scores than the C allele carriers, whereas among carriers of CHRNA5 rs3829787 CC genotype, ARRB2 rs1045280 TT carriers performed worse in RBANS. Our study identified for the first time an interactive effect between ARRB2 and CHRNA5 on cognitive function in MUD patients, which would enlarge our knowledge of genetic interaction on cognitive function.

Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients

Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients

ABC Family Gene Polymorphisms and Cognitive Functions Interact to Influence Antidepressant Efficacy.

The importance of identifying relevant indicators of antidepressant efficacy is highlighted by the low response rates to antidepressant treatment for depression. The ABC gene family, encoding ATP-dependent transport proteins facilitating the transport of psychotropic drugs, has drawn attention. This study delved into the relationship between antidepressant efficacy and seven single nucleotide polymorphisms of ABCB1 and ABCB6 genes. A total of 549 depressed patients participated in the study, and all completed a 6-week course of antidepressant treatment. Cognitive function was assessed at baseline and post-treatment. Patients were categorized based on post-treatment HAMD-17 scores (with HAMD≤7 indicating remission), and comparisons were made between different groups in terms of allelic gene frequencies and genotypes. Logistic regression was used to explore the interaction between cognitive function and genotype on efficacy. Dual-luciferase reporter assays were performed to compare the regulatory effects of rs1109866 allele variants on the ABCB6 promoter. There were no notable differences in allelic gene frequencies and genotypes between the remission and non-remission groups. Nonetheless, a significant interaction was identified between the rs1109866 genotype and language fluency-related indicators concerning efficacy (p=0.029) before correction. The dual-luciferase reporter assays demonstrated markedly higher fluorescence intensity of rs1109866-C compared to that of rs1109866-T (p<0.001). Relying solely on genetic polymorphisms of ABC family genes as predictors of antidepressant treatment response may not be sufficient. However, the interaction between the rs1109866 and cognition plays a pivotal role. The potentially enhanced transcriptional activity of rs1109866-C might offer insight into its impact on antidepressant efficacy.

PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from>1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R=0.55, P=3*10-9) and country gross domestic product (R=0.43, P=2*10-6) with overall population coverage varying between 5% in Estonia to<0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.

Polymorphisms in the Pfcrt, Pfmdr1, and Pfk13 genes of Plasmodium falciparum isolates from southern Brazzaville, Republic of Congo.

This study aimed to analyze polymorphisms in Pfcrt, Pfmdr1, and Pfk13 genes' markers of resistance to Artemisinin-based combination therapy (ACT), in Plasmodium falciparum isolates from southern Brazzaville, 15 years after the adoption of ACT in the Republic of Congo. A total of 369 microscopy-confirmed malaria-infected individuals were enrolled from March to October 2021 in the community and in health facilities during a cross-sectional study. The K76T mutation in the Pfcrt gene, N86Y and Y184F mutations in the Pfmdr1 gene were investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) while the codons region (1005-1300) of the Pfmdr1gene, and Pfk13 gene were sequenced. The prevalences of K76T, N86Y, Y184F mutations were 26.0%, 6.8%, and 27.7%, respectively. However, no mutations were detected in codons 1034, 1042, and 1246 of the Pfmdr1 gene. None of the mutations previously associated with artemisinin-based resistance were detected in the Pfk13 gene. The results reveal a significant decrease in the prevalence of K76T, N86Y, Y184F mutations, in Plasmodium falciparum isolates following the change of therapeutic policy. As artemisinin resistance is emerging throughout Africa, continued surveillance for early detection of these mutations and relevant partner markers of drug resistance are recommended in the Republic of Congo.

Effects of Genetic Polymorphism in the IFI27 Gene on Milk Fat Traits and Relevance to Lipid Metabolism in Bovine Mammary Epithelial Cells

Effects of Genetic Polymorphism in the IFI27 Gene on Milk Fat Traits and Relevance to Lipid Metabolism in Bovine Mammary Epithelial Cells

Computational analysis of the deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in TYR gene impacting human tyrosinase protein and the protein stability.

Tyrosinase, a copper-containing oxidase, plays a vital role in the melanin biosynthesis pathway. Mutations in the tyrosinase gene can disrupt the hydroxylation of tyrosine, leading to decreased production of 3,4-dihydroxyphenylalanine (DOPA). Consequently, this impairs the subsequent formation of dopaquinone, a key precursor in melanin pigment synthesis. This study aimed to identify the deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TYR gene that exert an influence on the human TYR protein. Additionally, we evaluated the impact of 10 FDA-approved drugs on the protein stability of mutated structures, exploring the potential for inhibitory pharmaceutical interventions. Through various bioinformatics tools, we detected 47900 nsSNPs, particularly K142M, I151N, M179R, S184L, L189P, and C321R, which were found to be the most deleterious variants, decreasing the protein stability. These drugs (Sapropterin, Azelaic Acid, Menobenzone, Levodopda, Mequinol, Arbutin, Hexylresorcinol, Artenimol, Alloin and Curcumin) interacted with the binding sites in four mutant models K142M, I151N, M179R, and S184L proving that these ligands directly bind with the active site of mutant tyrosinase protein to inhibit it's working. On the other hand, two mutant models L189P and C321R did not show any binding site residue interaction with any ligands. In conclusion, this in-silico analysis of deleterious nsSNPs in the TYR gene, coupled with the evaluation of ligands/drugs on mutated tyrosinase structures not only advances our understanding of molecular variations but also highlights promising pathways for targeted inhibitory interventions in the intricate network of melanin biosynthesis.

Effect of GH gene polymorphism on growth traits in goats of Meghalaya’s subtropical hilly region

Effect of GH gene polymorphism on growth traits in goats of Meghalaya’s subtropical hilly region

Assessment of dental caries severity in patients with VDR and СА12 polymorphisms

Background: There has been insufficient research into the genetic predisposition to dental caries. Research on the effect of gene polymorphisms on the incidence of dental diseases and the use of these findings in personalized prevention strategies are of high prognostic value. Aim: To assess the effect of VDR and СА12 polymorphisms on hard tooth tissues in young patients. Materials and Methods: The study examined 100 individuals, of which 59 (25 males and 34 females aged 23 to 25 years) were divided into groups based on the homozygous polymorphism: group 1 — VDR (n=19); group 2 — СА12 (n=32); and group 3 — combined VDR and CA12 (n=8). The DMF index was calculated in each group by fibreoptic transillumination method. Moreover, the pH of mixed saliva and serum 25(OH)D level (ng/mL) were measured. Results: In group 1, the DMF index was 15.11±0.15, with 25(ОН)D deficiency (17.4±0.7 ng/mL). In group 2, the DMF index was 16.99±1.43, with changes in the pH of saliva (6.80±0.01). In group 3, the DMF index was 17.92±1.37, with рН 6.30±0.11 and 25(ОН)D level of 13.7±0.4 ng/mL. Conclusion: Patients with VDR and СА12 polymorphisms had severe dental caries, acidic pH, and a deficiency of serum vitamin В metabolite.

Vascular Endothelial Growth Factor -460 C/T BstUI Gene Polymorphism is associated with Primary Open Angle Glaucoma

Vascular Endothelial Growth Factor -460 C/T BstUI Gene Polymorphism is associated with Primary Open Angle Glaucoma

Impact of PNPLA3 in Lean Individuals and in Cryptogenic Steatotic Liver Disease.

Although metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity, around 20% of individuals with hepatic steatosis may nonetheless have normal body mass index, a condition often referred to as lean nonalcoholic fatty liver disease (NAFLD). Under the new nomenclature and definition of MASLD, lean NAFLD can be further divided into lean MASLD (when there is one or more cardiometabolic risk factors) and cryptogenic steatotic liver disease (when there is no cardiometabolic risk factor). Current studies suggest that the at-risk PNPLA3 rs738409 variant is more common among individuals with lean NAFLD than their overweight and obese counterparts. However, even in this group, cardiometabolic risk factors are often required for the development of hepatic steatosis and liver injury. In the general population, PNPLA3 gene polymorphism is associated with an increased risk of MASLD, more severe liver histology (i.e., the presence of steatohepatitis and fibrosis) and future development of hepatocellular carcinoma and cirrhotic complications. Emerging data also suggest that individuals carrying the PNPLA3 GG genotype might have a greater reduction in hepatic steatosis and liver enzymes with lifestyle intervention and metabolic treatments, such as glucagon-like peptide-1 receptor agonists. Studies have not specifically examined the impact of PNPLA3 in lean individuals.

Potential Influence of Interleukin-6 -174G/C Gene Polymorphism on Kidney Graft Function and Tacrolimus Dose Requirements: Five-Year Follow-up

1.Introduction: The study aimed to investigate the influence of interleukin (IL)-6 -174G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation. 2.Methods: The study included 115 Caucasian kidney transplant recipients on Tac-based immunosuppression. The patients were followed between 6 and 60 post-transplantation months. Interleukin-6 and CYP3A5 genotyping were performed. 3.Results: Patients carrying the IL-6 -174GG genotype had lower eGFR values compared to the patients with the IL-6 -174GC and -174CC genotypes at the 12th, 48th and 60th post-transplantation months. The linear regression analysis indicated that eGFR at the 6th post-transplantation month and IL-6 -174G/C polymorphism are independent predictors of eGFR values in the late post-transplantation period. The IL-6 -174GG genotype carriers had lower dose-adjusted trough concentration (C0/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24th month), while this effect was independent of the CYP3A5 genotype within three years post-transplantation. 4.Conclusion: Interleukin-6 genotyping could be an additional tool to categorize patients toward the risk of graft deterioration in the long-term post-transplantation period. The IL-6 genotyping could be supportive in genotype-guided dosing of Tac.

Maternal alcohol consumption during pregnancy and child development: Role of ADH1B and ALDH2 gene polymorphisms-The Yamanashi Adjunct Study of the Japan Environment and Children's Study.

The role of polymorphisms in genes regulating alcohol metabolism, particularly those modulating the impact of prenatal alcohol exposure on the neurodevelopment of offspring, remains inconclusive. Herein, we aimed to determine the involvement of ADH1B and ALDH2 gene polymorphisms in maternal alcohol consumption during pregnancy and the risk of developmental delay in offspring in a Japanese population. We analyzed 1727 mother-child pairs from the Yamanashi Adjunct Study of the Japan Environment and Children's Study. Maternal alcohol consumption during pregnancy was determined through a mid-pregnancy questionnaire and categorized into three groups: never-drinkers, those who quit drinking in early pregnancy, and current drinkers. Developmental delays in children were assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3) at 3 years of age. We conducted a logistic regression analysis to explore the relationship between maternal drinking status during pregnancy and developmental delays in offspring with respect to maternal ADH1B (rs1229984) or ALDH2 (rs671) gene polymorphisms. Children born to mothers who continued alcohol consumption during pregnancy had a higher risk of delayed communication skills at 3 years of age compared with children born to mothers who did not drink alcohol (adjusted odds ratio [OR], 5.82; 95% confidence interval, 1.84-18.38). Analysis by ALDH2 gene polymorphism revealed that alcohol consumption by mothers carrying the wild-type ALDH2 (*1/*1) increased the risk of delayed communication skills at 3 years of age, whereas alcohol consumption by mothers carrying a heterozygotic genotype of ALDH2 (*1/*2) enhanced the risk of developmental delay in all five domains of the J-ASQ-3. The impact of ADH1B gene polymorphism could not be clearly elucidated. Our results suggest that alcohol consumption by pregnant females carrying the deficient variant ALDH2*2 genotype may increase the risk of developmental delay in their offspring.

Phenotypic and genotypic features of children with familial hypercholesterolemia

Dyslipidemia is a metabolic disorder in which the ratio of lipid particles in the blood changes. It is often associated with other conditions and diseases during childhood. Lipid metabolism disorders in children can be divided into two categories: primary, which are inherited from parents or occur de novo, and secondary, which occur during life. Familial hypercholesterolemia is the most common type of primary disorder, characterized by an increase in blood lipoprotein levels. However, the lipid composition in children with established familial hypercholesterolemia can vary. One factor that may contribute to higher lipid levels in these children is the presence of mutations in the apolipoprotein E gene.Purpose of the study was to investigate the phenotypic and genotypic features of children with familial hypercholesterolemia in order to better understand this condition.Materials and methods. Children with a clinical diagnosis of familial hypercholesterolemia underwent DNA sequencing to identify mutations in genes related to LDLR, APOB, LDLRAP1, and APOE genes.Results. Children with familial hypercholesterolemia most often carry the polymorphism c.388T&gt;C in the ApoE gene (g.45411941T&gt;C, p.Cys130Arg, rs429358). Also, 24.1% of children were found to be isolated carriers of various ApoE haplotypes, which are risk factors for dyslipidemia. In children with a pathogenic mutation characteristic of familial hypercholesterolemia and carriage of polymorphisms in the ApoE gene, the LDL level was statistically higher compared to non-carriers.Conclusion. Carriage of various polymorphisms in the ApoE gene in children with familial hypercholesterolemia may lead to an increase in the already elevated levels of LDL and total cholesterol.

Association between sleep quality and polymorphisms of the genes COMT, HTR2A and FKBP5 in individuals with and without dentofacial deformity

Sleep is a fundamental biological function, and any disturbances can lead to alterations in an individual’s physical, occupational, cognitive, and social functioning. Aim: This study aimed to evaluate the quality of sleep and its association with factors such as age, sex, facial profile, and genetic polymorphisms in individuals who underwent dental treatment. Methods: The study comprised a total of 227 individuals. The “Sleep Assessment Questionnaire” was utilized to evaluate sleep quality. For the genetic assessment, oral mucosa cells were collected and markers from the COMT (rs174675, rs165656), HTR2A (rs4941573, rs6313), and FKBP5 (rs1360780, rs3800373) genes were selected for real-time PCR analysis. The data were subjected to statistical analysis with a significance level of 0.05. Results: The results showed that women had a poorer perception of sleep quality (p&lt;0.05). There was a significant association between sleep quality and facial profile (p&lt;0.05). Individuals with facial profiles I and II had a poorer perception of sleep quality in general and in the domains of non-restorative sleep, sleep time disturbance, and restlessness. Individuals with facial profile II had a poorer perception of sleep apnea than those with profile III (p=0.034). There was a significant association between the COMT rs174675 polymorphism and restlessness (p=0.035). Conclusion: The poorest perception of sleep quality was associated with women and individuals with facial profiles I and II. The poorest perception of restlessness was associated with COMT rs174675 polymorphism.