CC Genotype Research Articles

Association of the Single Nucleotide Polymorphism 19216T/C in the TLR2 Gene (rs3804099) with Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii Infection Among Lebanese Children.

Toll-like receptors (TLRs), particularly the TLR2, take part in the elicitation of immune responses against Entamoeba histolytica. This study aimed to investigate the relationship between a specific polymorphism called rs3804099 in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children. A case-control study encompassed 180 participants including 68 children with amebiasis and 112 matched controls. Blood samples were collected, and genomic DNA was extracted using the classical proteinase K digestion and phenol-chloroform extraction method. The variant rs3804099 was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction. The accuracy of the genotyping was supported by sequencing 5% of samples. The TLR2 rs3804099 polymorphism was identified in the studied population, and the observed genotypic distributions were consistent with Hardy-Weinberg equilibrium (P > 0.05). The frequency of the rare CC genotype was significantly higher in patients compared to the noninfected group (P < 0.01). In controls, the homozygous TT genotype was less frequent than the heterozygous CT genotype. The rare CC genotype was associated with a higher risk of amebiasis among children (odds ratios = 3.27, P = 0.002). These findings provide evidence supporting the association between the rs3804099 SNP in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children.

The Evaluation of the Genetic Polymorphisms of TERT (rs2736100) and MUC5B (rs35705950) in Idiopathic Pulmonary Fibrotic patients

Background: Polymorphisms of the TERT and MUC5B genes have been consistently associated with idiopathic pulmonary fibrosis (IPF) in recent genome-wide genetic studies. In Iraq, we did not find research on the role of these polymorphisms in respiratory disorders, so we conducted this study to evaluate the genetic polymorphisms of TERT (rs2736100) and MUC5B (rs35705950) in IPF patients in Iraq. Method: The current study was a case-control study that included 70 patients who were diagnosed with IPF, in addition to, 70 healthy control groups who had no history or clinical evidence of IPF or asthma. blood samples from participants were obtained for DNA extraction, and T-ARMS-PCR was used to determine genetic polymorphisms of TERT (rs2736100) and MUC5B (rs35705950). Result: Current study showed that the mutant/minor homogenous genotype AA and allele A of TERT (rs2736100) appeared at a higher rate in patients (47% and 87% respectively) compared to control (38.5% and 53% respectively), as this indicator appeared as an effective factor (EF = 0.139 and 0.242 respectively), while the wild/major homogenous genotype CC and allele C were appeared in control at a rate of 38.5% and 50% respectively and in patients at rate 23% and 50% respectively. The results of MUC5B (rs35705950) G/T polymorphism showed that the mutant/minor TT genotype and T allele were associated with the occurrence of the disease (EF = 0.177 and 0.192 respectively) while the wild /major GG genotype and G allele appeared as a protective factor (PF= 0.243 and 0.375 respectively) for the control group. Moreover, most of the smoking patients were carriers of the mutant homogenous genotypes of TERT (rs2736100) and MUC5B (rs35705950). Conclusion: TERT (rs2736100) and MUC5B (rs35705950) polymorphisms are significantly associated with IPF, especially among smokers patients.

Analysis of angiotensin II type 1 receptor and osteoprotegerin gene polymorphism on the risk of cardiovascular mortality risk and progressivity of chronic kidney disease.

Chronic kidney disease (CKD) is a significant global public health issue with increased risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality. Single nucleotide polymorphisms (SNPs) on angiotensin II type 1 receptor (AT1R) A1166C and osteoprotegerin (OPG) C950T gene have received significant attention as a genetic risk factor for cardiovascular disease and CKD. This was a cross-sectional study involving 75 adults with CKD recruited from Nephrology Outpatient Clinics of Universitas Airlangga Hospital, Surabaya, Indonesia. Demographic data was obtained from interviews and medical records. The "CKD Patch" application was used to asses ASCVD and cardiovascular mortality risk scores. Statistical analysis was performed by using SPSS version 26. We detected four different AT1R gene polymorphisms (A1166C, A1160C, G1170T, and G1181C) and two OPG gene polymorphisms (T950C and G1181C) in Indonesian CKD patients. A1160C and G1181C polymorphisms were novel SNPs, newly discovered in this research. No significant association was found between AT1R SNPs and kidney prognostic markers or ASCVD risk/mortality risk scores. However, for OPG C950T we found that TT genotype had a significantly higher ACR than TC or CC genotype (P=0.032). As for OPG G1181C, we found that GG genotype had a higher serum creatinine and albumin to creatinine ratio compared to GC and CC genotypes (P=0.004 and 0.029, respectively). Genotype GC for OPG G1181C was also shown to be protective for having better kidney markers and lowest cardiovascular mortality risk compared to GG and CC genotypes (P=0.018 and 0.032, respectively). Increased ASCVD risk and mortality risk score was not found on individuals with AT1R gene SNPs. However, for OPG gene polymorphism, C950T and G1181C were associated with kidney progression and cardiovascular mortality.

Impact of UGT1A4 and UGT2B7 polymorphisms on lamotrigine plasma concentration in patients with bipolar disorder.

The purpose of this study was to evaluate the effect of UGT1A4 and UGT2B7 polymorphisms on the plasma concentration of lamotrigine in Chinese patients with bipolar disorder. A total of 104 patients were included in this study. Steady-state plasma lamotrigine concentrations were determined in each patient after at least 21 days of continuous treatment with a set dose of the drug. Lamotrigine plasma concentrations were ascertained using ultra-performance liquid chromatography. Simultaneously, plasma samples were used for patient genotyping. The age, sex, BMI, daily lamotrigine dose, plasma lamotrigine concentration, and lamotrigine concentration/dose ratio of patients exhibited significant differences, and these were associated with differences in the genotype [ UGT1A4 -142T>G and UGT2B7 -161C>T ( P < 0.05)]. Patients with the GG and GT genotypes in UGT1A4 -142T>G had significantly higher lamotrigine concentration/dose values (1.6 ± 1.1 and 1.7 ± 0.5 μg/ml per mg/kg) than those with the TT genotype (1.4 ± 1.1 μg/ml per mg/kg). Likewise, patients with the UGT2B7 -161C>T TT genotype had significantly higher lamotrigine concentration/dose values (1.6 ± 1.1 μg/ml per mg/kg) than those with the CC genotype (1.3 ± 1.3 μg/ml per mg/kg). Multiple linear regression analysis showed that sex, lamotrigine dose, UGT1A4 -142T>G, and UGT2B7 -161C>T were the most important factors influencing lamotrigine pharmacokinetics ( P < 0.001). The study results suggest that the UGT1A4 -142T>G and UGT2B7 -161C>T polymorphisms affect lamotrigine plasma concentrations in patients with bipolar disorder.

Betaine and B12 intake, glutathione concentration, and MTHFR, PEMT, and MTHFD1 genotypes are associated with diabetes-related parameters in Polish adults

BackgroundThere is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, DHFR (rs70991108) genotype, MTHFR (rs180113) genotype, MTHFD1 (rs2236225) genotype, PEMT (rs7946 and rs12325817) genotype with fasting glucose level insulin level, and diabetes related indices. MethodsThe study group consisted of 421 Polish adults aged 20–40 years old. Food intake was assessed using a three-day food diary. Plasma concentrations of choline, betaine, and TMAO were determined using ultra-high-performance liquid chromatography electrospray ionization mass spectrometry. Total plasma GSH level was measured using high-performance liquid chromatography. Insulin, folate and vitamin B12 concentrations were estimated using an enzyme-linked immunosorbent assay method. Genotyping was performed using TaqMan probes. ResultsGSH level was negatively associated with insulin (β = -0.11, p < 0.05) and gamma-glutamyltransferase (β = -0.12, p < 0.05), and positively associated with fasting glucose (β = 0.11, p < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = -0.13, p < 0.05) and HOMA-IR (β = -0.12, p < 0.05). Choline intake was negatively associated with insulin (β = -0.17, p < 0.01). Serum folate level was negatively associated with GGTP (β = -0.11; p < 0.05). The MTHFR CC genotype was associated with higher serum insulin level (β = 0.15; p < 0.01) and higher HOMA-IR (β = 0.15, p < 0.01), while the MTHFD1 AA genotype was negatively associated with QUICKI (β = -0.11, p < 0.05). ConclusionsOur findings suggest that higher GSHl higher intake of betaine, B12, and choline; as well as TT genotype of MTHFR and AA genotype of MTHFD1 are associated with lower diabetes-related parameters among adults.

The Possible Association of IL-6R Gene Polymorphisms in the Development of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN. This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients. Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05). The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.

Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.

Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine. Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90mmHg) and uncontrolled (BP greater than 140/90mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan® system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response. Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers. Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer.

In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection. The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls. No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001). The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

Frequency of rs35803318 single nucleotide polymorphism of ACE2 gene among the Kazakhs

In the article the results of genotyping of DNA samples obtained from the study participants on the single nucleotidepolymorphism (SNP) rs35803318 (C/T) of the ACE2 gene were presented. Genotyping was carriedout by real-time polymerase chain reaction (PCR) using the technique Amplification of the Refractory MutationSystem (ARMS). The frequencies of rs35803318 (C/T) genotypes and alleles in 96 representatives of theKazakh ethnic group living in the Karaganda region were analyzed. The ACE2 gene (angiotensin-convertingenzyme 2) was extensively investigated due to its role in susceptibility to infection by the SARS-CoV-2 viruscausing COVID-19. The ACE2 gene encodes a protein that serves as a receptor for the virus, and its variationscan affect a person's susceptibility to infection. The ACE2 protein plays a role in the regulation of angiotensinand the effect on blood pressure. Therefore, there is a link between ACE2 gene polymorphisms, includingrs35803318, and the development of cardiovascular diseases. According to the results of our study,the CT genotype (63.5 %) is the most common among Kazakhs, the CC genotype was 20.8 % and theTT genotype was 15.6 %. The distribution of polymorphism alleles is as follows: allele C — 52.6 %, allele A— 47.4 %.

Association of PPARGC1A gene polymorphism and mtDNA methylation with coal-burning fluorosis: a case–control study

BackgroundCoal-burning fluorosis is a chronic poisoning resulting from the prolonged use of locally available high-fluoride coal for heating and cooking. Prolonged fluoride exposure has been demonstrated to decrease PPARGC1A levels. Therefore, this case-control aims to evaluate the genetic association of PPARGC1A gene polymorphisms and methylation of the mitochondrial D-loop region with coal-burning fluorosis.ResultThe results showed that the TT genotype at rs13131226 and the AA genotype at rs1873532 increased the risk of coal-burning fluorosis (OR = 1.84, P = 0.004; OR = 1.97, P = 0.007), the CT and CC genotypes at rs7665116 decreased the risk of coal-burning fluorosis (OR = 0.54, P = 0.003). The TT genotype at the rs2970847 site and the AA genotype at the rs2970870 site increase the risk of developing skeletal fluorosis (OR = 4.12, P = 0.003; OR = 2.22, P = 0.011). Haplotype AG constructed by rs3736265-rs1873532 increased the risk of the prevalence of coal-burning fluorosis (OR = 1.465, P = 0.005); CG decreased the risk of the prevalence of coal-burning fluorosis (OR = 0.726, P = 0.020). Haplotype CGGT constructed by rs6821591-rs768695-rs3736265-rs2970847 increased the risk of the prevalence of skeletal fluorosis (OR = 1.558, P = 0.027). A 1% increase in CpG_4 methylation levels in the mtDNA D-loop region is associated with a 2.3% increase in the risk of coal-burning fluorosis. Additionally. There was a significant interaction between rs13131226 and rs1873532; CpG_4 and CpG_8.9; rs13131224,rs6821591 and rs7665116 were observed in the occurrence of fluorosis in the Guizhou population (χ2 = 16.917, P < 0.001; χ2 = 21.198, P < 0.001; χ2 = 36.078, P < 0.001).ConclusionPPARGC1A polymorphisms rs13131226 and rs1873532 and the mitochondrial DNA D-loop methylation site CpG_4 have been associated with an increased risk of fluorosis, conversely polymorphism rs7665116 was associated with a decreased risk of fluorosis. Polymorphisms rs2970870 were associated with increased risk of skeletal fluorosis, and polymorphism rs2970847 was associated with decreased risk of skeletal fluorosis. These SNPs and CpG can be used as potential targets to assess fluorosis risk.

Missense mutations in the CITED2 gene may contribute to congenital heart disease

BackgroundCongenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients.MethodsThree hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing.ResultsThe frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR.ConclusionThe samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and the etiology of the disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental and as-yet unidentified genetic contributors and their interactions. Previous research linked genetic variation on chromosome 6 to increased CRC risk. This region harbors multiple immune genes, including the gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand for the Natural Killer Group 2D receptor (NKG2D), a receptor expressed on Natural Killer (NK) cells and other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable CRC outcomes, we hypothesized that germline genetic variation in MICA could influence CRC risk. In a discovery set of 40,125 cases and controls, we show that the minor G allele at Chr6:31373718C>G (hg19) is associated with increased risk for CRC (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.04 - 1.15, p = 0.0009). The effect is stronger in EOCRC (OR = 1.26, 95% CI 1.08 - 1.44, p = 0.0023) than in those 50 and over (OR = 1.07, 95% CI 1.02 - 1.13; p = 0.012) (Ratio of ORs = 1.32, 95% CI 1.14 - 1.52, p = 0.0002). In an independent validation set of 77,983 cases and controls, the adjusted interaction by age-of-onset was significant at OR = 1.15 (95% CI 1.03 - 1.34, p = 0.0150) with a higher risk in EOCRC. Expression quantitative trait locus analysis in normal colonic epithelia showed that MICA RNA expression decreases linearly with each additional copy of the minor G allele (p = 3.345 × 10e-18). Bulk RNA analysis of the tumor immune microenvironment revealed that tumors from patients with CG or GG genotypes have lower resting and activated NK cell infiltration as compared to tumors from patients with CC genotype. Multiplex immunofluorescence analysis demonstrated that patients with a G allele (i.e. CG or GG genotype, but not CC genotype) have a statistically significant decrease in the number of NK cells in tumor compared to adjacent normal colonic mucosa. Taken together, population-based epidemiologic, molecular, genetic, cellular and immunologic evidence demonstrate that MICA genotype is associated with increased risk of EOCRC and reduced number of NK cells in colorectal tumors, suggesting that patients with a G allele have altered NK cell-mediated immunosurveillance. These novel findings suggest that EOCRC may have a previously unrecognized innate immune-mediated etiology which merits further investigation.

Identification of New Single Nucleotide Polymorphisms Potentially Related to Small Ruminant Lentivirus Infection Susceptibility in Goats Based on Data Selected from High-Throughput Sequencing.

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the infection. Antibodies against the virus can be detected in the blood of infected animals and are the main marker of infection. Additionally, in most infected animals, proviral DNA can also be detected, but at different levels. Due to the lack of treatment or vaccines, the most effective strategy to prevent SRLV infections are control programmes introduced by several countries based on the elimination of seropositive individuals from the flock. An alternative approach, which has currently become the rationale, is an identification of host factors which may predispose certain individuals or breeds to resistance or susceptibility to small ruminant lentivirus infection. In our work, attention was paid to goats of the Carpathian breed infected with SRLV. Available RNA-seq results from the blood of 12 goats with a determined level of SRLV proviral load were used to analyse single nucleotide polymorphisms (SNPs) by the variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) were selected for genotyping to determine their association with the level of small ruminant lentivirus proviral DNA in a group of 60 goats. Interestingly, in seronegative individuals, only the TT genotype of the PARP14 gene was observed, while the TMEM154 CC genotype was found only in seropositive goats. Both genes may be considered potential markers for resistance/susceptibility to SRLV infection. In contrast, polymorphisms identified in POU2AF1 and UBASH3A genes seemed to be deleterious for respective protein functions; therefore, these genes are less likely to be recognised as resistance/susceptibility markers of SRLV infection.

Association of the rs9896052 Polymorphism Upstream of GRB2 with Proliferative Diabetic Retinopathy in Patients with Less than 10 Years of Diabetes

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case–control study aimed to investigate the association between the rs9896052 polymorphism (A&gt;C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (&lt;10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17–6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Investigation of the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression

BackgroundThis study aimed to investigate the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression. Materials and methodsThis study included 88 patients diagnosed with prostate cancer and 91 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations. ResultsIn our study, the CC homozygous genotype of eNOS T786C gene variation was determined to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 2.343, 95%Cl: 0.990–5.544, p = 0.026), while the CT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was found to be significantly higher (OR: 0.589, 95%Cl: 0.325–1.068, p = 0.041). In addition, while the TT homozygous genotype of the eNOS G894T gene variation was found to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 9.068, 95%Cl: 4.396–18.777, p < 0.001), the GT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was determined significantly higher (OR: 0.227, 95%Cl: 0.121–0.427, p < 0.001). For eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT (p = 0.042) and bb-TT (p < 0.001) haplotype frequencies were significantly higher in the prostate cancer patient group, while aa-GT (p = 0.017), bb-GG (p = 0.049) and bb-GT (p < 0.001) haplotype frequencies were found to be significantly higher in the healthy control group. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype frequency was determined to be significantly higher in the patient group (p = 0.049), while the bb-CT haplotype frequency was determined to be significantly higher in the control group (p = 0.008). For eNOS (T786C -G894T) gene variations, TT-TT (p < 0.001) and CC-TT (p = 0.025) haplotype frequencies were found to be significantly higher in the patient group. On the other hand, TT-GT (p = 0.002) and CT-GT (p < 0.001) haplotype frequencies were determined to be significantly higher in the control group. The aa genotype of the intron 4 VNTR (4a/b) gene variation was determined to be significantly higher at Gleason score ≥7 compared to Gleason score <7 (OR: 0.184, 95%Cl: 0.050–0.677, p = 0.005). PSA levels were determined significantly higher in patients with Gleason score 7 and above (p = 0.008). The risk of developing prostate cancer was found to be significantly higher in patients carrying the CC homozygous mutant genotype of the eNOS T786C gene variation (p = 0.024) and in patients carrying the TT homozygous genotype of the G894T gene variation (p = 0.021). ConclusionsIn our study, the CC homozygous genotype of the eNOS T786C gene variation was determined as a genetic risk factor for the development of prostate cancer, while the CT heterozygous genotype was determined as a protective factor against prostate cancer. For the eNOS G894T gene variation, the TT homozygous genotype was determined as a genetic risk factor for the development of prostate cancer, while the GT heterozygous genotype was determined as a protective factor against prostate cancer. Additionally, for eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT and bb-TT haplotypes have been identified as genetic risk factors for the development of prostate cancer, while aa-GT, bb-GG and bb-GT haplotypes have been identified as protective factors against the disease has been determined. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype was determined as a genetic risk factor in the development of prostate cancer, while the bb-CT haplotype was determined as a protective factor against the disease. TT-TT and CC-TT haplotypes for eNOS (T786C -G894T) gene variations have been identified as genetic risk factors for the development of prostate cancer. In contrast, TT-GT and CT-GT haplotypes were found to be protective factors against the disease. The aa genotype of the intron 4 VNTR (4a/b) gene variation has also been identified as an important genetic risk factor in prostate cancer progression. Significantly increased PSA levels in patients with Gleason score 7 and above, and significantly increased PSA levels in patients carrying the CC and TT homozygous mutant genotype for T786C and G894T gene variations were determined as important risk factors. It is thought that the genetic biomarkers in our study may play a role as personalized therapeutic agents in slowing down the development of prostate cancer, increasing the effectiveness of treatment in prostate cancer, affecting the responses to drugs that regulate NO signaling, predetermining genetic predisposition to prostate cancer, and risk assessment in patients with prostate cancer.

Assessing the association between common functional Nuclear Factor Kappa-b gene polymorphisms (NFKB1, NFKBIZ, NFKBIA) and Alzheimer´s disease

The Nuclear Factor Kappa-b (NF-Κb) pathway has been implicated in the pathogenesis of Alzheimer´s disease (AD). We determined whether common variants in the NF-Κb genes were associated with the risk of developing late-onset AD (LOAD). A total of 639 Spanish LOAD and 500 controls were genotyped for the NFKB1 rs28362491/rs7667496, NFKBIA rs696, NFKBIZ rs3217713 and APOE-Ɛ2/3/4 polymorphisms. Rs7667496 C was increased in the patients (p<0.001) with the CC genotype showing a significant risk (CC vs T+, OR= 1.58, 95 %CI=1.25–2.01). The CC genotype was significantly associated with LOAD after correction by APOE-4+ genotypes, age and sex (p=0.0003, OR=1.88, 95 %CI=1.28–2.78). The NFKB1 rs28362491 I - rs7667496 C haplotype was significantly increased in the patients (p=0.02). NFKBIA and NFKBIZ variants were not associated with the risk of LOAD in our population. In conclusion, NFKB1 variants were associated with the risk of LOAD in our population. This finding encourages further studies to determine the involvement of the NF-kB components in LOAD.

Epistatic interactions between oxytocin- and dopamine-related genes and trust.

Trust is an essential human trait. Although research suggests that the interplay between oxytocinergic and dopaminergic systems affects trust formation, little research has focused on epistatic (i.e., gene by gene) interaction effects of oxytocin- and dopamine-related genes on trust. Using a sample of 348 adults (114 men), we aimed to investigate the associations between genetic variants in oxytocin- and dopamine-related genes and the general, neighborhood, and institutional trust with consideration of sex differences. Three-way interaction between oxytocin-related gene genotypes, dopamine-related genotypes, and sex was found for the oxytocin receptor gene (OXTR)rs1042778 and the Catechol-O-Methyltransferase gene (COMT) rs4680 genotypes (p = 0.02) and for OXTR rs2254298 and the dopamine D2 receptor gene (DRD2) rs1800497 genotypes (p = 0.01). Further sex-stratified analyses revealed that the interaction between OXTR rs1042778 and COMT rs4680 genotypes was associated with neighborhood trust among men (p = 0.0007). Also, the interaction between OXTR rs2254298 and DRD2 rs1800497 genotypes was associated with institutional trust among men (p = 0.005). Post-hoc analyses found that men with OXTR rs1042778 TG/TT and COMT rs4680 GG genotypes reported higher neighborhood trust than those with GG + AG/AA (B = 13.49, SE = 4.68, p = 0.02), TG/TT + AG/AA (B = 23.00, SE = 5.99, p = 0.001), and GG + GG (B = 18.53, SE = 5.25, p = 0.003). Similarly, men with OXTR rs2254298 AG/AA and DRD2 rs1800497 CC genotypes showed higher institutional trust than those with AG/AA + TT/TC (B = 15.67, SE = 5.30, p = 0.02). We could not find any interacting associations among women. While we note that our sample size and candidate gene approach have a potential risk of chance findings, our study provides an important foundation toward further exploration of sex-specific epistatic interaction effects of oxytocin- and dopamine-related genes on trust, indicating the importance of both systems in trust formation.

A synonymous mutation of rs1137070 cause the mice Maoa gene transcription and translation to decrease.

The Monoamine Oxidase-A (MAOA) EcoRV polymorphism (rs1137070) is a unique synonymous mutation (c.1409 T > C) within the MAOA gene, which plays a crucial role in Maoa gene expression and function. This study aimed to explore the relationship between the mouse Maoa rs1137070 genotype and differences in MAOA gene expression. Mice carrying the CC genotype of rs1137070 exhibited a significantly lower Maoa expression level, with an odds ratio of 2.44 compared to the T carriers. Moreover, the wild-type TT genotype of MAOA demonstrated elevated mRNA expression and a longer half-life. We also delved into the significant expression and structural disparities among genotypes. Furthermore, it was evident that different aspartic acid synonymous codons within Maoa influenced both MAOA expression and enzyme activity, highlighting the association between rs1137070 and MAOA. To substantiate these findings, a dual-luciferase reporter assay confirmed that GAC was more efficient than GAT binding. Conversely, the synonymous mutation altered Maoa gene expression in individual mice. An RNA pull-down assay suggested that this alteration could impact the interaction with RNA-binding proteins. In summary, our results illustrate that synonymous mutations can indeed regulate the downregulation of gene expression, leading to changes in MAOA function and their potential association with neurological-related diseases.

Association between rs4994 variant in β3-Adrenergic receptor and obesity in Vietnamese preschool-age children, independent of eating behaviors

BackgroundThe Arg64 allele of the rs4994 (Trp64Arg) variant in the β3-adrenergic receptor (ADRB3) gene is involved in the control of energy balance by altering lipolysis and thermogenesis in adipocytes, ultimately contributing to the development of obesity. The objective of our study was to investigate the association between the rs4994 variant of the ADRB3 gene and obesity in Hanoi preschool-age children, adjusting for their eating behaviors.MethodsA cross-sectional study was performed involving 708 children with normal weight and 304 children with obesity aged 3–5 years from 36 kindergartens in Hanoi, Vietnam. Cheek mucosa cell samples were used for DNA extraction, and genotyping at the ADRB3-rs4994 locus was performed using the polymerase chain reaction–restriction fragment length polymorphism method (PCR–RFLP). Eating behaviors were assessed using the Children’s Eating Behaviour Questionnaire (CEBQ). Binary logistic regression analysis was employed to examine the association between the rs4994 variant and obesity, adjusting for confounding factors such as age, sex, residence, birth weight, and eating behaviors.ResultsThe frequency of the C allele in the group with obesity was 16.4%, which was higher than in the control group (11.7%, P = 0.003). Children with the CC genotype exhibited significantly greater weight and weight-for-age Z-score compared to those with the TT and TC genotypes (P = 0.004 and 0.03, respectively). Following univariate and multivariate analyses adjusted for age, sex, residence, birth weight, and eating behaviors, a significant association between the rs4994 variant and obesity was observed (P < 0.05).ConclusionsThis study indicated that the ADRB3-rs4994 variant can be considered as an independent risk factor for obesity in Vietnamese preschool children.

IL-17 and IL-38 gene polymorphisms in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition commonly linked with Graves' disease (GD), characterized by orbital tissue inflammation and fibrosis. It is hypothesized that gene polymorphisms may influence production of the IL-17 and IL-38 cytokines, thereby impacting TAO development and progression. This study focused on investigating the gene polymorphisms of IL-17 (rs9463772 C/T in IL17F) and IL-38 (rs3811058 C/T, rs7570267 A/G in IL1F10) in patients with GD. A case-control study was conducted on 132 patients with TAO and 153 patients without TAO according to eligibility criteria. After clinical examination blood samples were collected for further investigations. Genotyping was performed with the TaqMan™ Master Mix kit. Allele and genotype frequencies were compared between studied groups and subgroups. No significant differences were found in age, duration of GD, or thyroid hormone between patients with and without TAO. However, a higher predisposition to develop TAO was observed among smokers (OR = 1.682, p = 0.03). Overall, no significant associations between gene polymorphisms and TAO development were identified in GD patients. Further analysis revealed that the CC genotype in IL1F10 rs3811058 polymorphism among Caucasians was associated with an increased risk of TAO (OR = 2.7, p = 0.02), as well as allele differences were also significant (OR = 2.8, p = 0.001). These findings shed light on TAO genetic predispositions in Kazakhstani GD patients, notably among Caucasians, underscoring the need for further research. These results may offer valuable targets for the development of novel treatments for TAO.