CC Genotype Research Articles

Pediatric pharmacogenetics: profiling CYP2C8 polymorphisms at King Abdulaziz University Dental Clinic.

Ibuprofen, a widely used non-steroidal anti-inflammatory (NSAID) for managing pain and inflammation in pediatric patients, is metabolized by the CYP2C8 enzyme. Studies suggest that the CYP2C8*2, *3, and *4 variations of the CYP2C8 gene diminish ibuprofen metabolism, increasing the risk of adverse reactions. The aim of this study was to determine the frequency of the CYP2C8*2, *3, and *4 alleles and genotypes in a pediatric population attending the King Abdulaziz University dental clinic and compare our findings to those of other populations. A cross-sectional study was conducted with 140 healthy Saudi children ages 6-12. Saliva samples were collected using Oragene™ DNA Sample Collection Kits and analyzed for polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study identified that CYP2C8*2 AA, AT, and TT genotypes occurred at frequencies of 87.86 %, 9.29 %, and 2.86 %, respectively. For CYP2C8*3, AA, AG, and GG genotypes were found in 87.14 , 8.75, and 4.29 % of subjects, respectively. The CYP2C8*4 allele was less frequent, with CC and CG genotypes at 97.86 % and 2.14 %, respectively, and the GG genotype was absent. Allele frequencies for CYP2C8*2, *3, and *4 were 7.5 %, 8.57 %, and 1.07 %, respectively. Our findings reveal that the allelic frequencies for the CYP2C8 polymorphisms in the Saudi pediatric cohort are substantially elevated compared to those reported in other Asian populations. This suggests Saudis may experience more varied drug responses, especially for medications that undergo metabolism by the CYP2C8 enzyme, like ibuprofen.

Contributions of Tissue Inhibitor of Metalloproteinase-1 Genotypes to the Risk of Metastasis in Gastric Cancer.

In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status. TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing. The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis. The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted.

Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?

Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.

Allele-specific micro-RNA-mediated regulation of ADAM33 in childhood allergic asthma.

A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms. Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression. Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper-responsiveness, lower FEV1% and higher dust mite-specific IgE activity compared to those with the CC genotype. miR-3928-5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR-3928-5p to the T allele was weaker, resulting in diminished negative regulation of protein expression. The rs3918400 SNP affects the negative regulation of ADAM33 by miR-3928-5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility.

TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.

TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known. We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses. >430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women. TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.

Polymorphism rs564398 of the ANRIL Gene as a Coronary-Artery-Disease-Associated SNP in Diabetic Patients of the Kazakh Population

Background/Objectives. A cardiovascular complication of type 2 diabetes mellitus like coronary artery disease is influenced by a complex interplay between environmental, phenotypic, and genetic factors. The genetic mechanisms in the development of this pathology are not established. This study aims to evaluate the association of polymorphisms rs1011970, rs62560775, and rs564398 from the 9p21.3 locus with coronary artery disease in diabetic patients of the Kazakh population. Methods. A total of 343 people participated in the case-control study: the control group consisted of 109 people with type 2 diabetes and coronary artery disease, while the control group included 234 people. Genotyping was performed using real-time PCR. Statistical analysis was carried out using Chi-square methods and calculating odds ratios (OR) with 95% confidence intervals (CI). Results. According to the results, only the rs564398 polymorphism of the ANRIL gene was associated with coronary artery disease (p = 0.04). The CC genotype increased the risk of developing coronary artery disease by more than 1.5 times (1.62 (1.02–2.56)), whereas the TT genotype reduced the risk of coronary artery disease (0.39 (0.17–0.91)). The remaining polymorphisms, rs1011970 and rs62560775, were not associated with coronary artery disease. Conclusions. Thus, this research further elicits the association of the ANRIL gene with cardiometabolic disease.

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.

Study on the relationship between KCNQ1 gene-environment interaction and abnormal glucose metabolism in the elderly in a county of Hechi City, Guangxi.

This study aimed to understand the potassium voltage-gated channel KQT-like subfamily, member 1 gene polymorphism in a rural elderly population in a county in Guangxi and to explore the possible relationship between its gene polymorphism and blood sugar. The 6 SNP loci of blood DNA samples from 4355 individuals were typed using the imLDRTM Multiple SNP Typing Kit from Shanghai Tianhao Biotechnology Co. The data combining epidemiological information (baseline questionnaire and physical examination results) and genotyping results were statistically analyzed using GMDR0.9 software and SPSS22.0 software. A total of 4355 elderly people aged 60 years and above were surveyed in this survey, and the total abnormal rate of glucose metabolism was 16·11 % (699/4355). Among them, male:female ratio was 1:1·48; the age group of 60-69 years old accounted for the highest proportion, with 2337 people, accounting for 53·66 % (2337/4355). The results of multivariate analysis showed that usually not doing farm work (OR 1·26; 95 % CI 1·06, 1·50), TAG ≥ 1·70 mmol/l (OR 1·19; 95 % CI 1·11, 1·27), hyperuricaemia (OR 1·034; 95 % CI 1·01, 1·66) and BMI ≥ 24 kg/m2 (OR 1·06; 95 % CI 1·03, 1·09) may be risk factors for abnormal glucose metabolism. Among all participants, rs151290 locus AA genotype, A allele carriers (AA+AC) were 0.70 times more likely (0.54 to 0.91) and 0.82 times more likely (0.70 to 0.97) to develop abnormal glucose metabolism than CC genotype carriers, respectively. Carriers of the T allele at the rs2237892 locus (CT+TT) were 0.85 times more likely to have abnormal glucose metabolism than carriers of the CC genotype (0.72 to 0.99); rs2237897 locus CT gene. The possibility of abnormal glucose metabolism in the carriers of CC genotype, TT genotype and T allele (CT + TT) is 0·79 times (0·67-0·94), 0·74 times (0·55-0·99) and 0·78 times (0·66, 0·92). The results of multifactor dimensionality reduction showed that the optimal interaction model was a three-factor model consisting of farm work, TAG and rs2237897. The best model dendrogram found that the interaction between TAG and rs2237897 had the strongest effect on fasting blood glucose in the elderly in rural areas, and they were mutually antagonistic. Environment-gene interaction is an important factor affecting abnormal glucose metabolism in the elderly of a county in Hechi City, Guangxi.

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI] 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

GJA4 gene inhibition may represent a potential target for novel antithrombotic therapies

Abstract The GJA4 gene encodes a protein called connexin 37, a component of gap junctions in vascular endothelial cells, crucial in regulating endothelial function and influencing inflammation, platelet adhesion and thrombus formation. This gene deletion in mice diminished thrombus formation in vitro in human blood. In these circumstances, connexin inhibition with pharmacological agents may represent potential avenues for developing novel antithrombotic agents. Aim To investigate whether the GJA4 rs618675 T&amp;gt;C variant is a risk factor for progressing atherosclerosis and cardiovascular (CV) events in an asymptomatic free of apparent CAD from a Portuguese population. Methods A prospective study was performed with 1421 individuals without apparent CV disease (73.6% male, aged 52.2±8.3 years) followed during an extended period of 7.2±5.1 years). GJA4 rs618675 T&amp;gt;C variant was genotyped by TaqMan real-time PCR technique (Applied Biosystems). Conventional, anthropometric, biochemical and clinical risk factors were studied. Bivariate analysis and multivariate Cox regression adjusted for age, gender, traditional risk factors, biochemical markers, and the genotypes under study was performed to determine which variables were, significantly and independently, associated with CV events. Kaplan-Meier's estimate assessed the prognosis. Results Bivariate analysis showed that 50.6% of wild genotype (TT) carriers had CV events vs. 66.2% without events. Of the risk genotype (CC) carriers, 10.1% had CV events, and 3.4% did not. After the Kaplan-Meier analysis, the TT carriers had 90% CV event-free survival time and the CC risk carriers had only 64% of event-free survival. Finally, after adjustment, CC genotype remained in the equation with an HR of 3.1 (p=0.003) and CT heterozygous with HR of 1.6 (p=0.043), together with Hypertension (HR 3.0; p&amp;lt;0.0001), Smoking habits (HR 2.3; p=0.001) and Diabetes (HR 1.9; p=0.015). Conclusion: The CC risk genotype of the GJA4 rs618675 represented an independent risk factor for progressing atherosclerosis and CV events in a Portuguese Population. Thrombus formation often begins with the adhesion of platelets to the endothelium, and connexin 37 may influence this process. The inhibition of connexin 37 emerges as a promising candidate for future cardiovascular prevention as well as for the development of new antithrombotic drugs.

Association of PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study

Abstract Background An increasing proportion of younger patients are currently hospitalized for acute myocardial infarction. Exploring the factors affecting coronary artery lesions and prognosis in patients with premature myocardial infarction (PMI) from a genetic perspective is of great significance to clinical management. Proprotein convertase subtilisins/kexins 6(PCSK6), a member of the PCSK family, functions in protein hydrolytic cleavage. It has been shown that PCSK6 polymorphisms are associated with carotid atherosclerosis. Purpose This research intended to evaluate the relationship between the PCSK6 rs1531817 polymorphism and the prognosis of PMI patients and their coronary stenosis. Methods This study was a prospective cohort study, which consecutively included 605 patients with PMI who underwent emergency PCI from January 2017 to August 2022 at X Hospital. Using the Massarray technique, the single nucleotide polymorphisms(SNPs) of PCSK6 rs1531817 were identified, and the patients underwent follow-up for 12 to 72 months, with major adverse cardiovascular events (MACEs) as the outcome. Analyze the relationship between patients' SNPs, Gensini score(GS), Triple vessel diseases(TVD), and MACEs. Results In PMI patients with PCSK6 rs1531817 CA+AA genotypes, ApoA1/ApoB levels were higher than in patients with CC genotype, and TC/HDL levels were lower (p &amp;lt; 0.05). Logistic regression analysis showed that the PCSK6 rs1531817 polymorphism (Dominant model: CA+AA vs.CC) was significantly correlated with the GS (high vs. low GS, adjOR=0.297, 95%CI:0.139-0.632, p=0.002; high vs. medium GS, adjOR=0.449, 95%CI:0.211-0.956, p=0.038), and it was correlated with the number of coronary artery lesions (TVD vs. SVD, adjOR=0.420, 95%CI:0.226-0.782, p=0.006; TVD vs. DVD, adjOR=0.406, 95%CI:0.214-0.773, p=0.006). According to multivariate Cox regression analysis, the PCSK6 rs1531817 dominant model was associated with the MACEs in PMI patients (adjHR=0.454, 95%CI:0.269-0.766, p=0.003). The mediation effect results showed that ApoA1/ApoB played a partially mediating role in the association between PCSK6 rs1531817 polymorphism and the severity of coronary stenosis (the effect leading to high GS and TVD accounted for 14.6% and 8.3% respectively), TC/HDL and TVD partially parallel mediated the association between PCSK6 rs1531817 polymorphism and MACEs (effect proportions were 8.1% and 17.1%, respectively). Conclusion Carrying the PCSK6 rs1531817 mutant A allele is an independent protective predictor of severe coronary stenosis and long-term prognosis in patients with PMI. Patients with the PCSK6 CA+AA genotypes have milder coronary stenosis partially because they have higher levels of ApoA1/ApoB; in addition, these patients have a better long-term prognosis partially because they have lower TC/HDL levels and fewer TVD patients.Figure 1.ApoA1/ApoB and TC/HDL were compareFigure 2.Correlation of PCSK6 rs1531817 pol

VDR gene polymorphisms rs731236 and rsS2228570 affect vitamin D levels in people of the Kaliningrad region

Vitamin D is an essential micronutrient that is involved in numerous biological processes. It not only keeps bones healthy, but also has a protective effect on the cardiovascular system, the pancreas and fatty tissue. Around 50% of the world’s population suffers from vitamin D deficiency or insufficiency. The prevalence of these diseases is significantly higher in obese people, regardless of age and place of residence. The presence of polymorphisms in the VDR gene (vitamin D receptor) can explain individual differences in the concentration of vitamin D 25(OH) in blood serum. Of particular interest are the effects of the polymorphisms rs731236 and rs2228570 on vitamin levels. Thus, the VDR polymorphism rs731236 is a synonymous substitution, whereas the polymorphism rs2228570 is a non-synonymous substitution. The article investigated the polymorphisms of the VDR gene rs2228570 (T/C), rs731236 (T/C) and determined their association with blood vitamin D levels in people from the Kaliningrad region with different body mass index (BMI). The material for the study was venous blood taken in the morning on an empty stomach from 232 people (mean age 50±13.5 years, 103 men and 129 women). The vitamin D content in the blood was determined by ELISA and the polymorphisms of the VDR gene were analyzed by PCR. In individuals with a BMI 30 kg/m2, changes in the lipid profile and liver function tests were recorded. The vitamin D level did not depend on the BMI of the study participants. Significant changes in blood vitamin D levels were found depending on the distribution of the VDR genotype. Vitamin D levels were higher in individuals with the CC genotype than in the TT and CT genotypes of the rs2228570 polymorphism and did not depend on BMI. In contrast, the presence of the rs731236 polymorphism in the VDR gene is associated with BMI. In obesity, vitamin D levels are therefore only reduced in people with the TT genotype of the rs731236 polymorphism, but not in people with the CC and TC genotype.

Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients

Background: Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. Methods: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. Results: Significant cognitive function differences were observed across SSD diagnostic categories (p &lt; 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (p = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (p = 0.01), with AG and GG associated with lower scores (p = 0.01 and p = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (p = 0.01). Conclusions: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies.

Gene polymorphisms of miR-323b and miR-1343 that regulate kininogen L are associated with schizophrenia susceptibility: A preliminary population‑based study.

miR-SNP is a type of functional single nucleotide polymorphism (SNP) that affects the regulatory functions of miRNA genes, miRNA binding sites, or components of miRNA biogenesis. This study aimed to explore the relationship between miRNA gene polymorphisms that regulate the kininogen L protein and schizophrenia (SCZ). Bioinformatics methods predicted miRNA gene polymorphism sites regulating the kininogen L protein. The polymorphisms of rs56103835, rs6513496, rs651349, and rs2986407 were detected using imLDR multiple SNP typing technologies in 513 SCZ patients and 509 controls. The association of miR-SNP variations with SCZ susceptibility and symptoms was evaluated using SNPstat to determine the optimal inheritance model. Generalized multifactor dimensionality reduction (GMDR) analysis and logistic regression were used to calculate miR-SNP interactions. The association between hsa-miR-323b-rs56103835 and SCZ was statistically significant under the dominant model. The result of gene-gene interaction showed that the three-factor model (rs56103835 / rs2986407 / rs2155248) was the best, but it could not be considered significantly related to SCZ. Additionally, SCZ patients with the CC or CT genotype on rs2986407 were more likely to experience auditory hallucinations than those with the TT genotype. Our data revealed that the mutation of hsa-miR-323b-rs56103835 from C to T was associated with susceptibility to SCZ. The mutation of hsa-miR-1343-rs2986407 from T to C increases the risk of auditory hallucinations in SCZ patients.

Milk traits characterization and association studies with DGAT1 polymorphisms in Bagnolese sheep.

The Bagnolese sheep is an authochtonous dual-purpose breed (milk and meat) reared in the Campania region, whose milk is used to produce Pecorino Bagnolese cheese. Genetic information on this sheep is extremely limited, especially regarding genes affecting productions. The aim of this study was to investigate milk production traits in Bagnolese sheep and the variability of diacylglycerol acyltransferase 1 (DGAT1) gene and its effects on milk production. Milk quantity was recorded during the morning milking, while Kjeldahl and Gerber methods were used to assess protein and fat percentage (w/v) of collected milk samples. Two PCR-RFLP protocols using BamHI and MspI endonucleases for genotyping of g.5553C>T and g.8539C>T at DGAT1 locus, respectively, were set up. Bagnolese sheep milk shows high fat and protein concentrations. Genotyping revealed a high frequency of the g.5553C and g.8539C alleles (0.56 and 0.95, respectively). The association study between the SNP g.5553C>T and milk traits showed that animals with the CT genotype had a higher percentage of fat produced per milking than those with the CC and TT genotypes (p<0.01). Similar results were found for protein yield percentage, with CT individuals being more productive than CC individuals (p<0.01). Bagnolese sheep milk parameters found are associated with high yields in the resulting dairy products. CT genotype at the SNP g.5553 of DGAT1 has shown a positive association with fat and protein milk yield percentage suggesting it could be considered a marker to improve productions of this breed. Finally, the new genotyping techniques used for this study enable a cheap and reliable characterization of two DGAT1 SNPs in sheep.

Association between genetic variants (rs2839698, and rs217727) in lncRNA H19 and Acute lymphoblastic leukemia susceptibility: a case-control study in the Iranian population

Leukemia is a cancer affecting the hematopoietic system with an unclear pathogenesis. Recent studies suggest a correlation between several long non-coding RNAs (lncRNAs) and leukemia development. This study focuses on the potential link between H19 (rs2839698 and rs217727) polymorphisms and Acute Lymphoblastic Leukemia (ALL) susceptibility. The study involved 150 patients with clinically confirmed ALL and 150 controls. This research included 150 Iranian patients, who were confirmed to have clinical ALL, and 150 healthy people as the control group. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. After adjusting for age using multivariate logistic regression analysis, individuals carrying the CT genotype of rs2839698 were found to have a significantly 0.32-fold reduced risk of ALL compared with carriers of the CC genotype. Furthermore, a significant 0.48-fold reduction in ALL risk was observed in patients with CT+TT genotype rs2839698 compared with CC. Moreover, the over-dominant model was applied to compare the CT genotype of rs2839698 with its CC+TT genotype, which showed a significant 0.36-fold reduction of ALL risk. Notably, the cases of ALL and the control group were not significantly different in terms of their genotype and allele frequencies of rs217727 polymorphism. Yet, the TT haplotype was significantly associated with ALL risk (OR: 1.64, p = 0.025). Following the findings of this study, it can be concluded that H19 SNP rs2839698, rather than rs217727, might act as an innovative susceptibility marker for ALL leukemia.

RNA-seq and whole-genome re-sequencing reveal Micropterus salmoides growth-linked gene and selection signatures under carbohydrate-rich diet and varying temperature

This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature.

Association of FSHR gene polymorphism with fertility of Holstein cows

Relevance. The view of the mechanisms of hormonal regulation of the ovarian cycle of cows has allowed the development of a large number of synchronization programs. An active search is underway for biomarkers related to the fertility of cows, as well as to identify animals with a high ovarian response to the injection of exogenous gonadotropins. The aim of the work is to study the polymorphism of the FSHR gene and its association with reproduction indicators in black-and-white Holstein dairy cows.Results. Based on the results of genotyping cows (n = 128) using the FSHR gene, the frequency of occurrence of the CC genotype was determined at the level of 0.601, the CG genotype — 0.360, GG — 0.031. It was found that for productive insemination, animals with the CG genotype require fewer inseminations. At the same age, the frequency of insemination of heifers with the CG genotype was 1.43, with the CC genotype — 1.60. After the first calving, the animals with the CG genotype responded more actively to hormonal stimulation in the postpartum period. The interval from the first to fruitful insemination in cows with the CG genotype was 34.7 days, in cows with the CC genotype — 57.2 days (p &lt; 0.05). The number of pregnant cows with the CG genotype re-inseminated after natural hunting was 2.1 times higher than the number of cows with the CC genotype (66.7% and 31.2%). It is assumed that exogenous hormone injection has a stimulating effect on the hypothalamus-pituitary-gonad system in cows with the CG genotype.

Predicting laboratory aspirin resistance in Chinese stroke patients using machine learning models by GP1BA polymorphism.

This study aims to use machine learning model to predict laboratory aspirin resistance (AR) in Chinese stroke patients by incorporating patient characteristics and single nucleotide polymorphisms of GP1BA and LTC4S. 2405 patients were analyzed to measure the Mutation frequency of GP1BA rs6065 and LTC4S rs730012. 112 patients with first-stroke arteriostenosis were prospectively enrolled to establish machine learning model. GP1BA rs6065 mutation frequency is 5.26% and LTC4S rs730012 is 14.78%. GP1BA rs6065 CT patients have more sensitivity to aspirin than CC genotype. Simple linear regression identified significant associations with age, smoking, HDL and GP1BA rs6065. Random forest (RF) and extreme gradient boosting (XGBoost) demonstrated predictive capabilities for AR. Findings suggest pre-identifying GP1BA rs6065 could optimize aspirin treatment, enabling personalized care and future research avenues.

Association between rs8192678 C/T polymorphism of the PPARGC1A gene and metabolically associated fatty liver disease in obese children living in the Moscow region

Over the past 30 years, the incidence of childhood obesity has quadrupled, leading to a rise in metabolically associated fatty liver disease (MAFLD), which has multifactorial genesis. Numerous studies highlight a significant genetic contribution to the development and severity of MAFLD. Purpose of the study. Тo determine the distribution of alleles and genotypes of the rs8192678 C/T polymorphism of the PPARGC1A gene and its relationship with the development of MAFLD in obese children living in the Moscow region. Materials and methods. The study included 87 children with exogenous constitutional obesity. The children were divided into two groups: group I - obesity without MAFLD (n = 43), group II - obesity with MAFLD (n = 44). The association of genotypes with the risk of developing MAFLD was studied in various genetic models. Results. 43 (49.4%) children had genotypes containing the T allele: 4 (4.6%) - homozygous TT genotype, 39 (44.8%) - heterozygous CT genotype. The CC genotype was detected in 44 (50.6%) children. The frequency of allele C was 73%. Carriers of the T allele have almost twice the risk of developing MAFLD than сarriers of the C allele (OR = 2.08 (95% CI: 1.05-4.24), p = 0.041). Conclusion. Тhe rs8192678 polymorphism increases the risk of developing MAFLD already in childhood, and with the homozygous TT genotype, this risk more than doubles. Studying the genetic contribution to the development of MAFLD enables a comprehensive approach to assessing individual risks of each patient.