Influence Of Gene Polymorphisms Research Articles

Genotypic Influences on Actuators of Aerobic Performance in Tactical Athletes

Background: This study examines genetic variations in the systemic oxygen transport cascade during exhaustive exercise in physically trained tactical athletes. Research goal: To update the information on the distribution of influence of eleven polymorphisms in ten genes, namely ACE (rs1799752), AGT (rs699), MCT1 (rs1049434), HIF1A (rs11549465), COMT (rs4680), CKM (rs8111989), TNC (rs2104772), PTK2 (rs7460 and rs7843014), ACTN3 (rs1815739), and MSTN (rs1805086)—on the connected steps of oxygen transport during aerobic muscle work. Methods: 251 young, healthy tactical athletes (including 12 females) with a systematic physical training history underwent exercise tests, including standardized endurance running with a 12.6 kg vest. Key endurance performance metrics were assessed using ergospirometry, blood sampling, and near-infrared spectroscopy of knee and ankle extensor muscles. The influence of gene polymorphisms on the above performance metrics was analyzed using Bayesian analysis of variance. Results: Subjects exhibited good aerobic fitness (maximal oxygen uptake (VO2max): 4.3 ± 0.6 L min−1, peak aerobic power: 3.6 W ± 0.7 W kg−1). Energy supply-related gene polymorphisms rs1799752, rs4680, rs1049434, rs7843014, rs11549465, and rs8111989 did not follow the Hardy–Weinberg equilibrium. Polymorphisms in genes that regulate metabolic and contractile features were strongly associated with variability in oxygen transport and metabolism, such as body mass-related VO2 (rs7843014, rs2104772), cardiac output (rs7460), total muscle hemoglobin content (rs7460, rs4680), oxygen saturation in exercised muscle (rs1049434), and respiration exchange ratio (rs7843014, rs11549465) at first or secondary ventilatory thresholds or VO2max. Moderate influences were found for mass-related power output. Conclusions: The posterior distribution of effects from genetic modulators of aerobic metabolism and muscle contractility mostly confirmed prior opinions in the direction of association. The observed genetic effects of rs4680 and rs1049434 indicate a crucial role of dopamine- and lactate-modulated muscle perfusion and oxygen metabolism during running, suggesting self-selection in Swiss tactical athletes.

Influence of the Brain-Derived Neurotrophic Factor Gene Polymorphism on Weight Loss Following Intragastric Balloon Intervention: A Cross-Sectional Study.

There is noticeable heterogeneity in weight loss outcomes following intragastric balloon (IGB) treatment, with average weight loss ranging between 11% to 15% of total body weight. Genetic variations associated with obesity have been found to influence weight loss response, however such variations are limited. Therefore, the aim of this study is to investigate the impact of the obesity associated brain-derived neurotrophic factor (BDNF) gene polymorphism rs11030104 with weight loss outcomes following IGB treatment. In this cross-sectional study, BDNF rs11030104 was analysed in 106 individuals who underwent intragastric balloon treatment. Weight loss metrics were evaluated at the three-month follow-up: percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), and percentage of body mass index loss (%EBMIL). The effects of additive and dominant genetic models were evaluated. Both linear and logistic regression were applied to assess associations between rs11030104 genotypes and weight loss metrics. A total of 71 participants completed the 3-month follow-up assessment (loss to follow-up: 33%). This study found a significant association between the BDNF rs11030104 polymorphism and weight loss. A-allele carriers showed a better response to IGB treatment. Individuals carrying the AA genotype were found to have a greater %TWL than those carrying the GG genotype at 3 months post-IGB treatment (11.05% vs 5.09%, p=0.003). Our results suggest that BDNF rs11030104 influences the response to weight loss after IGB treatment and therefore could be added to the growing list of genetic variants that predict greater weight loss response.

The association of gene polymorphisms of adenosine and dopamine receptors with the response to caffeine citrate treatment in infants with apnea of prematurity: a prospective nested case-control study

BackgroundTo investigate the potential influence of adenosine and dopamine receptor genes polymorphisms in combination with clinical factors on the response of preterm infants to caffeine citrate treatment in apnea of prematurity (AOP).MethodsA prospective nested case-control study enrolled 221 preterm infants with gestational age < 34 weeks. These infants were divided into the response (n = 160) and the non-response groups (n = 61). 22 single-nucleotide polymorphisms in adenosine and dopamine receptor genes were genotyped. The basic characteristics and clinical outcomes of the two groups were compared. Univariate logistic regression analysis was performed to evaluate the differences in genotype distribution between the groups. Multivariable logistic regression analysis was performed to identify independent risk and protective factors and develop a nomogram to predict caffeine citrate response in preterm infants.ResultsPreterm infants in the non-response group had lower gestational age, lower birth weight, longer periods of oxygen supplementation and caffeine citrate use, and higher incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), neonatal respiratory distress syndrome (NRDS), retinopathy of prematurity (ROP), and brain injury (P < 0.05 for all). The ADORA1 rs10920573, ADORA2B rs2015353, ADORA3 rs10776728, DRD3 rs7625282, and DRD3 rs6280 gene polymorphisms were associated with caffeine citrate response in preterm infants (PFDR < 0.05 for all). The ADORA1 rs10920573 CC (aOR, 3.51; 95% CI, 1.34–9.25) and DRD3 rs6280 CT genotypes (aOR, 3.19; 95% CI, 1.53–6.65) were independent risk factors for non-response, whereas greater gestational age (aOR, 0.631; 95% CI, 0.53–0.75) was an independent protective factor for response. The concordance index of the nomogram was 0.764 (95% CI, 0.687–0.842), and the calibration and decision curve analysis indicated the nomogram had excellent predict performance.ConclusionsAdenosine receptor gene and dopamine receptor gene polymorphisms influence caffeine citrate treatment response in AOP. By combining genetic and clinical variables, it is possible to predict the response to caffeine citrate treatment in preterm infants.

Influence of Prematurity and Glutation S-Transferase Gene Polymorphisms on the Degree of Asthma Control in Children

Influence of Prematurity and Glutation S-Transferase Gene Polymorphisms on the Degree of Asthma Control in Children

The Influence of Genetics and Gene Polymorphism on Biological Complications for Dental Implant Survival: A Review.

The objective of this review is to expose the main genetic changes and genetic polymorphisms that may or may not be associated with greater susceptibility to reduced survival of dental implants and, consequently, to their loss. Case-control studies that fully portrayed the specific types of genetic polymorphisms that may be associated with dental implant failure were included by searching in the PubMed, Scopus, and Web of Science databases from 2010 to 2023. The following descriptors and their combinations in English were used to search for articles: "dental implants," "bone genes," "genetics," "polymorphism genetics," "genetic risk factor," and "interleukin." The initial search resulted in 107 results (PubMed n = 47, Scopus n = 14, and Web of Science n = 46). After a manual search, reviewing each article's title and abstract, and excluding duplicates, systematic reviews, and literature reviews, 30 articles were selected. After reading these 30 articles in full, 18 studies that did not describe the specific genetic polymorphism in relation to dental implant survival were excluded. Therefore, 12 articles were included in this review. The genetic polymorphisms of interleukin (IL)-1A, IL-1B, IL-4, IL-6, IL-10, IL-1 receptor antagonist, tumor necrosis factor-α, receptor activator of nuclear factor kappa B legend, and cluster of differentiation 14 were analyzed in the included studies. In seven of the studies, a statistically significant correlation between genetic polymorphisms and dental implant failure was observed. Of the polymorphisms studied, IL-1A (-899), IL-1B (+3954), and IL-4 (+33) showed a greater association with dental implant loss.

The influence of P2Y12 gene polymorphisms on clopidogrel therapy in patients after percutaneous coronary intervention.

Aim: We aimed to define the influence of P2Y12 polymorphisms (rs6801273, rs2046934, and rs6809699), diabetes, hypertension, obesity, hypercholesterolemia, statins intake, and smoking habit on clopidogrel therapy in patients undergoing percutaneous coronary intervention.Materials & methods: We used PCR-RFLP and PCR-ASO for P2Y12 genotype analysis. The effectiveness of the therapy was measured with the VerifyNow method and defined in platelet reactivity units.Results: Studied polymorphisms had no statistically significant influence on PRU before (PRU0) and 6 months (PRU6) after the procedure. H1/H1 diabetic carriers had significantly higher PRU6 values than patients without diabetes. Obese H1/H2 subjects had significantly lower PRU6 values than H1/H2 non-obese carriers.Conclusion: We found that obesity and diabetes may influence the long-term outcome of antiplatelet therapy.

DRD4 gene polymorphism and impulse control disorder induced by dopamine agonists in Parkinson's disease.

Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this retrospective study, we analyzed a cohort of Parkinson's disease patients treated with dopamine agonists and investigated the influence of the dopamine D4 receptor gene polymorphism, DRD4 7R+, which is linked to psychiatric disorders, impulsive traits, and addictive behaviors. We found that DRD4 7R+ is a significant genetic risk factor associated with the severity of ICD.

Association of RAN and RANBP2 Gene Polymorphisms With Glioma Susceptibility in Chinese Children.

Glioma is the most prevalent pediatric central nervous system malignancy. RAN, member RAS oncogene family (RAN), is a key signaling molecule that regulates the polymerization of microtubules during mitosis. RAN binding protein 2 (RANBP2) is involved in DNA replication, mitosis, metabolism, and tumorigenesis. The effects of RAN and RANBP2 gene polymorphisms on glioma susceptibility in Chinese children are currently unknown. This study aimed to evaluate the association between RAN and RANBP2 gene polymorphisms and glioma susceptibility in Chinese children. We recruited 191 patients with glioma and 248 children without cancer for this case-control study. Polymerase chain reaction-based TaqMan was applied to gene sequencing and typing. Logistic regression model-calculated odds ratio and 95% confidence interval were used to verify whether the gene polymorphisms (RAN rs56109543 C>T, rs7132224 A>G, rs14035 C>T, and RANBP2 rs2462788 C>T) influence glioma susceptibility. Based on age, gender, tumor subtype, and clinical stage, stratified analyses of risk and protective genotypes were conducted. p values for mutant genotype analyses were all >0.05, indicating no significant correlation between these gene polymorphisms and glioma risk. RAN and RANBP2 gene polymorphisms were not found to be statistically significantly associated with glioma susceptibility in Chinese children. Other potential functional gene polymorphism loci of RAN and RANBP2 will need to be evaluated in the search for novel glioma biomarkers.

Особливості виникнення поширеного перитоніту та вплив поліморфізму гена 5,10-метилентетрагідрофолатредуктази

It is relevant in modern surgery to clarify the risk factors of widespread peritonitis and to improve the treatment and diagnostic algorithms for the management of such patients. Aim - to establish the features of the occurrence of widespread peritonitis and the influence of MTHFR gene polymorphisms on the risk of its occurrence. Materials and methods. The study included 100 patients who underwent surgical interventions for acute abdominal diseases complicated by peritonitis: acute appendicitis (48%), acute cholecystitis (32%), perforated ulcer of the stomach or duodenum (8%), tumor perforation (3%), injuries of the abdominal cavity (3%), pinched hernia (2%) and intestinal obstruction (4%). Genotypes of MTHFR gene polymorphisms rs1801131 and rs1801133 were determined by real-time polymerase chain reaction. Mathematical processing of the research results was carried out using the Statistica 10 program. Results. The risk of disseminated peritonitis was increased with perforated gastric or duodenal ulcer, tumor perforation, abdominal trauma, herniated hernia, or intestinal obstruction compared with acute appendicitis and cholecystitis. The risk of disseminated peritonitis was lower in II blood group carriers compared and was associated with temperature at hospitalization and pulse rate. Conclusions. The factors determining the risk of disseminated peritonitis in the multivariate regression model were the diagnosis, heart rate, and the rs1801131 genotype of the MTHFR gene. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Identification of the polymorphism of the &lt;i&gt;APAF1&lt;/i&gt; gene and its association with economically useful traits of Holstein cattle

A decrease in the reproductive ability of cows leads to losses in dairy farming, as dairy production decreases due to the lack of a lactation period in cows. Haplotype HH1 is responsible for a mutation in the protein apoptotic protease-activating factor 1 (APAF1), as a result of which its structure is shortened, resulting in a decrease in fertility, an increase in the number of embryonic mortality and abortions in Holstein dairy cattle. To study the polymorphism of the APAF1 gene (SNP p.Q579X [c.1741C&gt;T]) and its associations with economically traits, we used data and DNA from 254 cows of Holstein population of indigenous selection of Breeding Farm Integrated Agricultural Production Center of the Republic of Tatarstan. As a result, 2 alleles (Q and X) and 2 genotypes (QQ and QX) were identified in the APAF1 – BstC8 I gene locus in cattle. It was established that the dominant population is represented by carriers of the homozygous QQ genotype of the APAF1 gene - 98.0 %, and the frequency of the Q allele reached 0.990. The percentage of QX-type animals is minimal - 2.0 % of the total number of cows subjected to the study, as a result of which the occurrence of the X allele was only 0.010. An assessment of the influence of APAF1 gene polymorphism on economically significant traits showed that, depending on the genotype, such reproduction traits as the age of the first fertile insemination, the duration of the dry period and the Doha fertility index vary statistically significantly. Analysis of dairy productivity traits that cows with the QQ genotype are significantly superior to individuals with the QX genotype in all compared positions, with the exception of the content of the mass fraction of fat. Through selection using genetic marking, damage to livestock farms can be reduced by reducing the frequency of carriers of lethal alleles in the parent generation. This research was supported by FASO Russia project, registration number 122011800138-7.

Influence of apolipoprotein E gene polymorphisms on coronary artery disease in patients undergoing coronary angiography

ObjectivePrevious studies have shown that apolipoprotein E (ApoE) gene polymorphisms have an impact on coronary artery disease(CAD). However, many studies have small sample sizes and different conclusions. The purpose was to retrospectively study the influence of ApoE gene polymorphisms on CAD. MethodsThis study assessed the influence of different ApoE genotypes on coronary heart disease in patients who received coronary angiography and used multivariate logistic regression to assess the influence of different ApoE genotypes on CAD. ResultsPatients with different ApoE genotypes had no obvious differences in the incidence of hypertension, diabetes or obesity（P > 0.05). Patients with ε2/ε2 had higher incidence of hypertriglyceridemia than patients with other ApoE genotypes, while patients with ε3/ε3 had a lower incidence of hypertriglyceridemia than those with ε3/ε4,ε4/ε4, ε2/ε3 and ε2/ε2（P < 0.05）. Patients with ε3/ε4, ε4/ε4, ε3/ε3 and ε2/ε2 had no significant differences in the severity or incidence of CAD （P > 0.05). ε2/ε4 and ε2/ε3 reduced the risk of high LDL-C, and reduced the severity and incidence of coronary heart（P < 0.05). ε2/ε3 reduced risk of premature coronary artery disease（PCAD）（P < 0.05). ε2/ε3 reduced risk of CAD in patients age <45,age at 60–74 and age ≥74, while ε2/ε4 reduced risk of CAD in patients age ≥74（P < 0.05). ConclusionPatients with ε3/ε4, ε4/ε4,ε3/ε3 and ε2/ε2 had no significant differences in the severity and occurrence of CAD. Compared to the isoform ε3 (ε3/ε3), isoform ε4 did not increased the severity and occurrence of CAD. Compared with ApoE other genotypes, ε2/ε3 and ε2/ε4 reduced the risk of high LDL-C and the severity and occurrence of CAD.

Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with clear cell RCC (ccRCC) being the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of HVEM and CD160 gene polymorphisms on ccRCC susceptibility and patient overall survival (OS) over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, as well as two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within HVEM SNPs rs8725 and rs1886730 is also associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of ccRCC. Moreover, rs1886730 was found to be associated with OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as OS.

Evaluating the Influence of the ACTN3 rs1815739 Gene Polymorphism on the Performance of Physically Active Adult Males in the Arrowhead Agility Drill Test

The alpha actinin-3 gene (ACTN3) is a significant candidate gene among genetic markers that determine athletic ability. The ACTN3 gene is responsible for the creation of the actin protein in fast-twitch muscle fibers, which is associated with muscle power and speed. The objective of this study was to analyze the changes in performance of the arrowhead agility drill test and the distribution of genotype variants in the ACTN3 rs1815739 gene polymorphism in physically active adult males after a 6- week training period. The research will focus on a cohort of 58 male students, aged 19-24, who are enrolled in the Faculty of Sports Sciences and participate in swimming activities. Genomic DNA was extracted from swab samples obtained from participants using the Buccalyse DNA Extraction Kit from Isohelix, following the manufacturer's supplied technique. The study findings revealed that there was no statistically significant difference between all three genotypes when comparing the pre-test and post-test values of the sample group in terms of left and right foot characteristics. Within this framework, it is acknowledged that the outcomes derived from our investigation could potentially influence the research findings. These aspects include the restricted sample size and the incapacity to regulate individual variances such as concentration and motivation during the pre-test and post-test sessions. Nevertheless, it is believed that the results obtained from our study could potentially enhance future research and literary works in the same field.

Analysis of the effect of CYP2C19 gene properties on the anti-platelet aggregation of clopidogrel after carotid artery stenting under network pharmacology

Antiplatelet therapy is an important factor influencing the postterm patency rate of carotid artery stenting (CAS). Clopidogrel is a platelet aggregation inhibitor mediated by the adenosine diphosphate receptor and is affected by CYP2C19 gene polymorphisms in vivo. When the CYP2C19 gene has a nonfunctional mutation, the activity of the encoded enzyme will be weakened or lost, which directly affects the metabolism of clopidogrel and ultimately weakens its antiplatelet aggregation ability. Therefore, based on network pharmacology, analyzing the influence of CYP2C19 gene polymorphisms on the antiplatelet therapeutic effect of clopidogrel after CAS is highly important for the formulation of individualized clinical drug regimens. The effect of the CYP2C19 gene polymorphism on the antiplatelet aggregation of clopidogrel after CAS was analyzed based on network pharmacology. A total of 100 patients with ischemic cerebrovascular disease who were confirmed by the neurology department and required CAS treatment were studied. CYP2C19 genotyping was performed on all patients via a gene chip. All patients were classified into the wild-type (WT) group (*1/*1), heterozygous mutation (HTM) group (CYP2C19*1/*2, CYP2C19*1/*3), and homozygous mutation (HMM) group (CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3). High-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) was used to detect the blood concentration of clopidogrel and the plasma clopidogrel clearance (CL) rate in different groups of patients before and after clopidogrel treatment. The platelet aggregation rate of patients with different genotypes was measured by turbidimetry. The incidences of clopidogrel resistance (CR) and stent thrombosis in different groups after three months of treatment were analyzed. The results showed that among the different CYP2C19 genotypes, patients from the HTM group accounted for the most patients, while patients from the HTM group accounted for the least patients. Similarly, the clopidogrel CL of patients in the HMM group was lower than that of patients in the WT group and HTM group (P < 0.01). The platelet inhibition rate of patients in the HMM group was evidently inferior to that of patients in the WT group and HTM group (P < 0.01). The incidence of CR and stent thrombosis in the WT group was notably lower than that in the HTM and HMM groups (P < 0.01). These results indicate that the CYP2C19 gene can affect CR occurrence and stent thrombosis after CAS by influencing clopidogrel metabolism and platelet count.

Influence of a polymorphic genes combination on the risk of developing intestinal infections, induction of regulatory and effector peptides

Background. The high incidence rate, the severity and the occurrence of complications determine the relevance of intestinal infections today. The individual’s immune response, which is controlled by the polymorphism of inflammatory protein genes is significant in the development and course of the disease. This issue in relation to intestinal infections has been understudied and is of interest in researching the influence of gene polymorphism on the development of intestinal infections.The aim. To establish the presence of an associative relationship between the set of IL-2 T330G and TLR-4 ASP299GLY polymorphic genes and the likelihood of developing an acute intestinal infection, as well as the role of a combination of genes in induction of inflammatory proteins.Materials and methods. The study included 108 people with acute intestinal infection and 94 apparently healthy volunteers. To determine the concentration of cytokines, immunoglobulins, we used blood serum and Vector-Best (Koltsovo, Russian Federation) test systems. The polymorphism of the IL-2 T330G and TLR-4 ASP299GLY genes was determined by PCR using Litekh LLC (Moscow, Russian Federation) primers. Statistical analysis was carried out using the ICMJE (International Committee of Medical Journal Editors) principle and SAMPL (Statistical Analyses and Methods in Published Literature) recommendations by MS Excel 2010 (Microsoft Corp., USA) and Statistica 6.0 (StatSoft Inc., USA) software.Results. When constructing the ROC curve, the area under the curve was within 0.77, sensitivity – 0.9, specificity – 0.5 (95% confidence interval: 0.7–0.84; p &lt; 0.001). These results are at a good prognostic level with a high risk of the disease development. Comparing the level of pro-inflammatory and anti-inflammatory cytokines, immunoglobulins between the patients with -299А/А+-330GG haplotype of TLR4 ASP299GLY and IL-2 T330G genes and the carriers of only the dominant allele A of the TLR4 A/A299 genotype or only the minor allele G of IL-2 G/G330 we found no significant differences (p ≥ 0.05).Conclusion. Among carriers of the -299А/А+-330GG haplotype of the TLR4 ASP299GLY and IL-2 T330G genes, the risk of the intestinal infection development increases, but this haplotype does not affect the production of inflammatory molecules.

The influence of drug-induced metabolic enzyme activity inhibition and CYP3A4 gene polymorphism on aumolertinib metabolism

The purpose of this study is to clarify the drug interaction profile of aumolertinib, and the influence of CYP3A4 genetic polymorphism on aumolertinib metabolic characteristics. Through microsomal enzyme reactions, we screened 153 drugs and identified 15 that significantly inhibited the metabolism of aumolertinib. Among them, telmisartan and carvedilol exhibited potent inhibitory activities in rat liver microsomes (RLM) and human liver microsomes (HLM). In vivo, the pharmacokinetic parameters of aumolertinib, including AUC and Cmax, were significantly altered when co-administered with carvedilol, with a notable decrease in the clearance rate CLz/F. Interestingly, the pharmacokinetic parameters of the metabolite HAS-719 exhibited a similar trend as aumolertinib when co-administered. Mechanistically, both telmisartan and carvedilol exhibited a mixed-type inhibition on the metabolism of aumolertinib. Additionally, we used a baculovirus-insect cell expression system to prepare 24 recombinant CYP3A4 microsomes and obtained enzymatic kinetic parameters using aumolertinib as a substrate. Enzyme kinetic studies obtained the kinetic parameters of various CYP3A4 variant-mediated metabolism of aumolertinib. Based on the relative clearance rates, CYP3A4.4, 5, 7, 8, 9, 12, 13, 14, 17, 18, 19, 23, 24, 33, and 34 showed significantly lower clearance rates compared to the wild-type. Among the different CYP3A4 variants, the inhibitory potency of telmisartan and carvedilol on the metabolism of aumolertinib also varied. The IC50 values of telmisartan and carvedilol in CYP3A4.1 were 6.68 ± 1.76 μM and 0.60 ± 0.25 μM, respectively, whereas in CYP3A4.12, the IC50 exceeded 100 μM. Finally, we utilized adeno-associated virus to achieve liver-specific high expression of CYP3A4*1 and CYP3A4*12. In the group with high expression of the less active CYP3A4*12, the magnitude of the drug-drug interaction was significantly attenuated. In conclusion, CYP3A4 genetic polymorphism not only influences the pharmacokinetic characteristics of aumolertinib, but also the inhibitory potency of telmisartan and carvedilol on it.

#1625 Influence of polymorphisms in genes for interleukin-6 and interleukin-10 on dialysis patients survival

Abstract Background and Aims Chronic inflammation is an important non-traditional risk factor for morbidity and mortality in patients with terminal kidney disease. Associated occurrence of malnutrition, inflammation and atherosclerosis was observed in patients on dialyses and marked as MIA syndrome, a vicious circle in which pro inflammatory cytokines play a key role. It is known that there were individual differences in creation of cytokines, and it is assumed that polymorphisms in the promoter regions of cytokine genes can have a key role in the predisposition to chronic inflammation and its consequences. We investigated association between interleukin-6 -174 G&amp;gt;C, interleukin-10 -1082 G&amp;gt;A, inteleukin-10 -819 T&amp;gt;C genotypes with the survival of patients with terminal renal failure. Method In this study, a total of 128 patients were examined, 77 on the regular hemodialysis (HD) and 51 on the peritoneal dialysis (PD) program of the UKCS Nephrology Clinic in Belgrade. Age, gender, BMI, duration of HD/PD, C-reactive protein (CRP), albumin and IL-6 and IL-10 concentration in serum were analyzed. Analysis of IL6 -174G&amp;gt;C and IL10 -819T&amp;gt;C polymorphisms was performed by the allele-specific PCR method, and analysis of the IL10 -1082G&amp;gt;A polymorphism by the PCR/RFLPs method. The patients were followed for 36 months and during that time 37 patients died. Results Univariate analysis showed that significant predictors of mortality were age (OR= 1.16,95%CI 1.061-1.269, p=0.001), albumin concentration (OR= 0.81, 95%CI 0.656-0.999, p=0.049), CRP (OR= 1.06, 95%CI 1003-1.124, p=0.039) and IL-6 (OR= 1.12, 95%CI 1.038-1.216, p=0.004), as well as IL-6176G&amp;gt;C gene polymorphism (OR= 0.82, 95%CI 0.097-0.805, p=0.018), while in multivariate logistic model separated only the concentration of IL-6 and the polymorphism in the gene for IL-6 -174 G&amp;gt;C. Estimated arithmetic mean of survival in subjects with the IL-6 -174GG genotype was 33.1 months (95%CI 30.8-35.3), GC 34.6 months (95% CI 33.6-35.7) and CC 26.1 (95% CI 20.0-32.2). There is statistically significant difference in survival time in relation to IL-6 -174 G&amp;gt;C genotype (chi-square=11.398; p=0.003). Estimated arithmetic mean survival in patients with the IL-10 -1082 GG genotype was 32.6 months (95% CI 30.5-35.2), in GA 31.5 (95% CI 29.2-33.8) and in AA 36.0 (95% CI 35.9-36.1). Exists statistically significant difference in survival time in relation to 1082G&amp;gt;A genotype (chi-square=9.669; p=0.008). Conclusion Monitoring of survival in 128 patients during 36 months showed that significant worse survival was experienced in patients with IL -6 -174 CC genotype, while polymorphisms in IL 10 gene-1082 G&amp;gt;A and -819T&amp;gt;C did not significantly affect survival. In this group of patients, beside IL-6-174 CC genotype, concentrations of IL-6, C reactive protein and albumin were significant predictors of mortality as well as Kt/V.

TLR9 gene polymorphism confers risk to Helicobacter pylori infection in Jiangsu, China and its inspiration for precision nursing car.

The number of studies which investigate the association between TLR9 gene polymorphism and Helicobacter pylori (H.pylori) infection is low and their results are not consistent. To get a better understanding of the association between TLR9 gene polymorphism and H.pylori infection, providing basis and risk assessment for precision nursing for hospital nurses. A total of 630 normal physical examination subjects were collected including 240 H.pylori (+) and 390 H.pylori (-) subjects. PCR-RFLP was applied to investigate the present polymorphism. At the same time, the meta-analysis was performed between TLR9 gene polymorphism and H.pylori infection risk. Three genotypes (TT, TC, and CC) were observed for TLR9 gene rs187084 polymorphism. CC genotype and C allele were responsible for the significant associations (all P< 0.05). Meta-analysis found no significant associations were found by any genetic models (all P> 0.05). TLR9 polymorphism has a crucial role in H.pylori infection risk and CC genotype confers increased risk to H.pylori infection in the Southern Chinese population. After understanding the influence of TLR9 gene polymorphism on H.pylori infection, nurses can improve the risk assessment of Helicobacter pylori infection and provide health education more personally.

The Influence of CYP2C19 Gene Polymorphism on Selective Serotonin Reuptake Inhibitors In Patients with Major Depressive Disorder: A Pharmacogenetic Prospecting Approach

Major Depressive Disorder (MDD) is a chronic disorder characterized by at least a two-week-long major depressive episode. Selective Serotonin Reuptake Inhibitors (SSRIs) remain the primary prescribed antidepressants to treat MDD. However, SSRIs themselves are found to be ineffective in some individuals or may even lead to adverse side effects. These variable responses have been linked to the drug being metabolized by CYP2C19, which exhibited various polymorphisms. Understanding how gene polymorphism affects drug metabolism is essential since these insights can revolutionize clinical practice, allowing for more precise and personalized treatment approaches that optimize efficacy while minimizing side effects. This issue is particularly pertinent in Indonesia, where research in this area lags behind the pressing need for such studies. In this review, the impact of CYP2C19 polymorphism on the effectiveness of SSRI class drugs, namely citalopram, escitalopram, and sertraline, are explored. Nine relevant articles related to the topic have been studied in Japan, China, Turkey, Russia, Scandinavia, and Australia. The results concluded that CYP2C19 polymorphism can influence the metabolism of SSRIs (citalopram, escitalopram, and sertraline) due to its variability in enzyme activities, which includes both loss-of-function (*2, *3) and gain-of-function (*17) polymorphisms. Consequently, these genetic variations can lead to significant changes in drug efficacy and safety changes within individual patients. This review sheds light on the importance of considering genetic factors when prescribing SSRIs for MDD in the future treatment strategies.

Longitudinal study investigating the influence of COMT gene polymorphism on cortical thickness changes in Parkinson's disease over four years

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting over 3% of those over 65. It's caused by reduced dopaminergic neurons and Lewy bodies, leading to motor and non-motor symptoms. The relationship between COMT gene polymorphisms and PD is complex and not fully elucidated. Some studies have reported associations between certain COMT gene variants and PD risk, while others have not found significant associations. This study investigates how COMT gene variations impact cortical thickness changes in PD patients over time, aiming to link genetic factors, especially COMT gene variations, with PD progression. This study analyzed data from 44 PD patients with complete 4-year imaging follow-up from the Parkinson Progression Marker Initiative (PPMI) database. Magnetic resonance imaging (MRI) scans were acquired using consistent methods across 9 different MRI scanners. COMT single-nucleotide polymorphisms (SNPs) were assessed based on whole genome sequencing data. Longitudinal image analysis was conducted using FreeSurfer's processing pipeline. Linear mixed-effect models were employed to examine the interaction effect of genetic variations and time on cortical thickness, while controlling for covariates and subject-specific variations. The rs165599 SNP stands out as a potential contributor to alterations in cortical thickness, showing a significant reduction in overall mean cortical thickness in both hemispheres in homozygotes (Left: P = 0.023, Right: P = 0.028). The supramarginal, precentral, and superior frontal regions demonstrated significant bilateral alterations linked to rs165599. Our findings suggest that the rs165599 variant leads to earlier manifestation of cortical thinning during the course of the disease. However, it does not result in more severe cortical thinning outcomes over time. There is a need for larger cohorts and control groups to validate these findings and consider genetic variant interactions and clinical features to elucidate the specific mechanisms underlying COMT-related neurodegenerative processes in PD.