The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis.

BACKGROUND: Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. METHODS: Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 µM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. RESULTS: In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. CONCLUSION: MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

Examining the relationship between genetic polymorphisms (BDKRB2, GNB3, HIF1A, MCT1, NOS3) and endurance athlete status.

PURPOSE: Genetic factors are important in terms of athletic performance. Recent studies to determine the relationship between the genes that lead to physiological responses have attracted attention. In this respect, this meta-analysis study was designed to examine the relationship between genetic polymorphism (BDKRB2 rs5810761, GNB3 rs5443, HIF1A rs11549565, MCT1 rs1049434, NOS3 rs2070744) and endurance athlete's status. METHODS: The search included studies published from 2009 to 2022. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned. Only case-control studies were included in the meta-analysis. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned, and a total of 31 studies met the criteria for inclusion in the meta-analysis. Relevant data from the included studies were collected and analyzed using a random effects or fixed effects model. The effect size was calculated as the odds ratio or a risk ratio the corresponding 95% confidence intervals. RESULTS: According to the results of the analysis, BDKRB2 rs5810761 + 9 allele, and NOS3 rs2070744 T allele were significantly more prevalent in endurance athletes (p < 0.05). Genotype distributions of BDKRB2 rs5810761, MCT1 rs1049434, and NOS3 rs2070744 showed significant differences in the dominant model (p < 0.05). However, no significant association was found between endurance athlete status and GNB3 rs5443 and HIF1A rs11549465 polymorphisms. CONCLUSION: These results show that some gene polymorphisms play an important role in endurance athlete status and suggest that having a specific genetic basis may also confer a physiological advantage for performance.

Single-Nucleotide Polymorphism in Genes Encoding G Protein Subunits GNB3 and GNAQ Increase the Risk of Cardiovascular Morbidity among Patients Undergoing Renal Replacement Therapy.

Single-nucleotide polymorphisms in G protein subunits are linked to an increased risk of cardiovascular events among the general population. We assessed the effects of GNB3 c.825C > T, GNAQ -695/-694GC > TT, and GNAS c.393C > T polymorphisms on the risk of cardiovascular events among 454 patients undergoing renal replacement therapy. The patients were followed up for a median of 4.5 years after the initiation of dialysis. Carriers of the TT/TT genotype of GNAQ required stenting because of coronary artery stenosis (p = 0.0009) and developed cardiovascular events involving more than one organ system (p = 0.03) significantly earlier and more frequently than did the GC/TT or GC/GC genotypes. Multivariate analysis found that the TT/TT genotype of GNAQ was an independent risk factor for coronary artery stenosis requiring stent (hazard ratio, 4.5; p = 0.001), cardiovascular events (hazard ratio, 1.93; p = 0.04) and cardiovascular events affecting multiple organs (hazard ratio, 4.9; p = 0.03). In the subgroup of male patients left ventricular dilatation with abnormally increased LVEDD values occurred significantly more frequently in TT genotypes of GNB3 than in CT/CC genotypes (p = 0.007). Our findings suggest that male dialysis patients carrying the TT genotype of GNB3 are at higher risk of left ventricular dilatation and that dialysis patients carrying the TT/TT genotype of GNAQ are prone to coronary artery stenosis and severe cardiovascular events.

GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine.

Background: Immune responses following vaccination against COVID-19 with different vaccines and the waning of immunity vary within the population. Genetic host factors are likely to contribute to this variability. However, to the best of our knowledge, no study on G protein polymorphisms and vaccination responses against COVID-19 has been published so far. Methods: Antibodies against the SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured 1 and 6 months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against the SARS-CoV-2 spike protein were measured in a group of 597 participants 1 month after the second vaccination with mRNA-1273. Genotypes of GNB3 c.825C>T were determined in all participants. Results: The median antibody titer against the SARS-CoV-2 spike protein and median values of spots increment in the SARS-CoV-2 IFN-γ ELISpot assay against the S1-peptide pool were significantly decreased from months 1 to 6 (p < 0.0001). Genotypes of GNB3 c.825C>T had no influence on the humoral immune response. At month 1, CC genotype carriers had significantly increased T-cell responses compared to CT (p = 0.005) or TT (p = 0.02) genotypes. CC genotype carriers had an almost 6-fold increased probability compared to TT genotype carriers and an almost 3-fold increased probability compared to T-allele carriers to mount a SARS-CoV-2-specific T-cell response above the median value. Conclusion: CC genotype carriers of the GNB3 c.825C>T polymorphism have an increased T-cell immune response to SARS-CoV-2, which may indicate better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.

Integrated bioinformatics analysis and screening of hub genes in polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders, posing a serious threat to the health of women. Herein, we aimed to explore new biomarkers and potential therapeutic targets for PCOS by employing integrated bioinformatics tools. METHODS: Three gene expression profile datasets (GSE138518, GSE155489, GSE106724) were obtained from the Gene Expression Omnibus database and the differentially expressed genes in PCOS and normal groups with an adjusted p-value < 0.05 and a |log fold change (FC) | > 1.2 were first identified using the DESeq package. The weighted correlation network analysis (WGCNA) R package was used to identify clusters of highly correlated genes or modules associated with PCOS. Protein-protein interaction (PPI) network analysis and visualization of genes in the key module were performed using the STRINGdb database and the NetworkX package (edge > 5), respectively. The genes overlapping among the key module genes and PCOS-associated genes were further analyzed. Ligand molecules with strong binding energy < -10 kJ/mol to GNB3 were screened in the drug library using MTiOpenScreen. AutoDock, ChimeraX, and BIOVIA Discovery Studio Visualizer were further used to elucidate the mechanism of ligand interaction with GNB3. Finally, the relationship between GNB3 and PCOS was verified using experimental models in vivo and in vitro. RESULTS: Of the 11 modules identified by WGCNA, the black module had the highest correlation with PCOS (correlation = 0.96, P = 0.00016). The PPI network of 351 related genes revealed that VCL, GNB3, MYH11, LMNA, MLLT4, EZH2, PAK3, and CHRM1 have important roles in PCOS. The hub gene GNB3 was identified by taking the intersection of PCOS-related gene sets. MTiOpenScreen revealed that five compounds interacted with GNB3. Of these five, compound 1 had the strongest binding ability and can bind amino acids in the WD40 motif of GNB3, which in turn affects the function of the G protein-coupled receptor ß subunit. GNB3 was also significantly downregulated in PCOS models. CONCLUSION: We identified the hub gene GNB3 as the most important regulatory gene in PCOS. We suggest that compound 1 can target the WD40 motif of GNB3 to affect related functions and must be considered as a lead compound for drug development. This study will provide new insights into the development of PCOS-related drugs.

GNB3 c.825C>T (rs5443) Polymorphism and Risk of Acute Cardiovascular Events after Renal Allograft Transplant

The c.825C>T single-nucleotide polymorphism (rs5443) of the guanine nucleotide-binding protein subunit ß3 (GNB3) results in increased intracellular signal transduction via G-proteins. The present study investigated the effect of the GNB3 c.825C>T polymorphism on cardiovascular events among renal allograft recipients posttransplant. Our retrospective study involved 436 renal allograft recipients who were followed up for up to 8 years after transplant. The GNB3 c.825C>T polymorphism was detected with restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The GNB3 TT genotype was detected in 43 (10%) of 436 recipients. Death due to an acute cardiovascular event occurred more frequently among recipients with the TT genotype (4 [9%]) than among those with the CC/CT genotypes (7 [2%]; p = 0.003). The rates of myocardial infarction (MI)−free survival (p = 0.003) and acute peripheral artery occlusive disease (PAOD)−free survival (p = 0.004) were significantly lower among T-homozygous patients. A multivariate analysis showed that homozygous GNB3 c.825C>T polymorphism exerted only a mild effect for the occurrence of myocardial infarction (relative risk, 2.2; p = 0.065) or acute PAOD (relative risk, 2.4; p = 0.05) after renal transplant. Our results suggest that the homozygous GNB3 T allele exerts noticeable effects on the risk of MI and acute PAOD only in the presence of additional nonheritable risk factors.

The GNB3 c.825C>T (rs5443) polymorphism and protection against fatal outcome of corona virus disease 2019 (COVID-19).

Background and aims: Albeit several factors which influence the outcome of corona virus disease (COVID-19) are already known, genetic markers which may predict the outcome of the disease in hospitalized patients are still very sparse. Thus, in this study, we aimed to analyze whether the single-nucleotide polymorphism (SNP) rs5443 in the gene GNB3, which was associated with higher T cell responses in previous studies, might be a suitable biomarker to predict T cell responses and the outcome of COVID-19 in a comprehensive German cohort. Methods: We analyzed the influence of demographics, pre-existing disorders, laboratory parameters at the time of hospitalization, and GNB3 rs5443 genotype in a comprehensive cohort (N = 1570) on the outcome of COVID-19. In a sub cohort, we analyzed SARS-CoV-2-specific T cell responses and associated GNB3 rs5443 genotypes. We investigated the influence of all factors on COVID-19 fatality in multivariable analysis. Results: We found a younger patient age, normotension or absence of diabetes mellitus or cardiovascular diseases, normal blood cell counts, and low inflammatory markers at hospital admission were protective factors against fatal course of disease. In addition, the rs5443 TT genotype was significantly associated with protection against COVID-19 fatality (OR: 0.60, 95% CI: 0.40-0.92, p = 0.02). We also observed significantly increased SARS-CoV-2-specific T cell responses in rs5443 TT genotype carriers (p = 0.01). Although we observed a significant association of the factors described previously in univariate analysis, only a younger age of the patients, normal blood cell counts, and the GNB3 rs5443 TT genotype remained independent predictors against COVID-19 fatality in multivariable analysis. Conclusion: Immutable predictors for COVID-19 fatality are relatively rare. In this study we could show that the TT genotype of the SNP rs5443 in the gene GNB3 is associated with protection against COVID-19 fatality. It was as well correlated to higher SARS-CoV-2-specific T cell responses, which could result in a milder course of disease in those patients. Based on those observations we hereby provide a further prognostic biomarker, which might be used in routine diagnostics as a predictive factor for COVID-19 mortality already upon hospitalization.

Endothelium function biomarkers and carotid intima-media thickness changes in relation to NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphism in the essential arterial hypertension.

Objective. The aim of the present study was to clarify the endothelial function biomarkers and carotid "intima media" thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 - control) participated in the case-control study. Soluble vascular cell adhesion molecule (sVCAM-1), total NO metabolites (NO2 -+NO3 -), transcriptional activity of NOS3 gene, endothelium-dependent flow-mediated dilation of the brachial artery (FMD BA), and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO - 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene - 46.03% 7 times (p<0.001), and become higher sVCAM-1 - 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT - 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries - 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity - 34.54% (p=0.003). Atherosclerotic plaques were unilateral - 24.77% (χ2=5.35; p=0.021) or bilateral - 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters - 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.

Vof16-miR-205-Gnb3 axis regulates hippocampal neuron functions in cognitively impaired diabetic rats.

BACKGROUND: Diabetes is a chronic metabolic disease and an independent risk factor for cognitive damage. Non-protein coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are involved in various pathophysiological conditions. METHODS: In this study, cognitive impairment was induced in diabetics rats by streptozotocin (STZ) injection, and the differential lncRNAs and mRNAs in rat hippocampal tissue between control and STZ-treated groups were analyzed with microarray. RESULTS: In the hippocampus of STZ-treated diabetic rats, lncRNA Vof-16, and Gnb3 mRNA were significantly upregulated and silicon analysis showed that Vof-16 and miR-205 share the same miRNA response element (MRE). In addition, the overexpression of Vof-16 in primary hippocampal neurons inhibited the expression of miR-205, and vice versa. Dual luciferase assay verified the binding between Vof-16 and miR-205, and Vof-16 was seen to promote the proliferation of primary hippocampal neurons via sponging miR-205. Silicon analysis predicted that miR-205 could bind with Gnb3, which was verified with dual luciferase assay, and the overexpression of miR-205 could inhibit the protein level of Gnb3, which could be rescued by co-expression with Vof-16. In conclusion, lncRNA Vof-16 regulated Gnb3 expression by competitively binding to miR-205. CONCLUSIONS: These results provided a novel regulation axis for the pathogenesis of STZ-induced diabetes.

Meta-analysis of the genetic association between maternal GNB3 C825T polymorphism and risk of pre-eclampsia.

BACKGROUND: The relationship between the C825T polymorphism of GNB3 (encoding G-protein ß3 subunit) and pre-eclampsia risk is unclear. OBJECTIVE: To systematically explore the association between GNB3 C825T and pre-eclampsia. SEARCH STRATEGY: PubMed, EMBASE, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI) databases were searched to September 1, 2020, using keywords including "GNB3 C825T" and "pre-eclampsia". SELECTION CRITERIA: Case-control and cohort studies investigating the relationship between GNB3 C825T polymorphism and pre-eclampsia were included. DATA COLLECTION AND ANALYSIS: Two reviewers collected the data independently and calculate odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: The meta-analysis involved eight studies from seven publications, including 2071 cases and 3419 controls. Overall analysis showed that GNB3 C825T was associated with increased pre-eclampsia risk in the recessive model (OR, 1.21; 95% CI, 1.01-1.44; P = 0.04). Subgroup analysis stratified by Hardy-Weinberg equilibrium revealed a relationship between GNB3 C825T and increased risk of pre-eclampsia in the allelic (OR, 1.66; 95% CI, 1.34-2.05; P < 0.001), homozygous (OR, 2.12, 95% CI, 1.04-4.32; P  = 0.04), dominant (OR, 1.91; 95% CI, 1.18-3.11; P = 0.009), and recessive (OR, 1.70; 95% CI, 1.03-2.81; P = 0.04) models. CONCLUSIONS: Maternal GNB3 C825T polymorphism seems to be a risk factor for pre-eclampsia.

G protein gene variants in schizophrenia

Abstract Background Various studies demonstrating enhanced vulnerability to apoptosis may contribute to the pathobiology of schizophrenia. Objective Thus, G proteins may provide an intriguing link between the signal transduction, and apoptotic hypotheses of schizophrenia. In the light of these findings, we investigated whether G protein gene polymorphisms (GNAS1-T393C and GNB3-C825T) accounted for an increased risk of schizophrenia. Methods The present analyses were based on 100 subjects diagnosed with schizophrenia, and on 100 unrelated healthy controls. The genotyping of GNAS1-T393C, and GNB3-C825T gene polymorphisms were performed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Results: We demonstrated the positive association of GNB3-C825T gene variants with schizophrenia risk (p: 0.023). In our study, more prevalent CC genotype frequencies were detected in GNB3 in patients compared with the frequencies in the controls. The individuals with GNB3-C825T CC genotype had 2 fold increased risk for schizophrenia (p: 0.011, c2: 6.39, OR:2.14, 95% CI: 1.18-3.90). Discussion Our study results suggested that GNB3-C825T polymorphism might be associated with schizophrenia.

Upper Gastrointestinal Sensitization And Symptom Generation.

Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders, and their diagnostic criteria are symptom-based, with the absence of anatomical and biochemical abnormalities of the gastrointestinal tract. Chronic visceral symptoms are common both in patients with an identifiable organic disease but also in FGID patients. Patients suffering from upper gastrointestinal functional disorders typically present with various symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, and epigastric pain. Considering their increasing prevalence, difficulties in diagnosis, and low quality of life, FGIDs have become an emerging problem in gastroenterology. We aimed to provide an updated summary of pathways involved in visceral sensitization. We examined the recent literature searching for evidence of the most important studies about the mechanisms underlying gastrointestinal symptom generation and sensitization.

Comprehensive insight into functional interaction between GNB3 C825T and eNOS T-786C, G894T gene polymorphisms and association with susceptibility to diabetic erectile dysfunction.

BACKGROUND: No study has assessed the possible involvement of endothelial nitric oxide synthase (eNOS) T-786C and G894T and G-protein ß3 subunit (GNB3) C825T polymorphisms with susceptibility to diabetic vasculogenic erectile dysfunction (VED) in North African subjects. OBJECTIVES: Our aim was to evaluate the interaction and association between these gene polymorphisms and this disorder. MATERIALS AND METHODS: A total of 164 type 2 diabetes patients with VED diagnosed with penile color Doppler ultrasonography and 148 age-matched healthy volunteers were genotyped for the rs1799983 (G894T) and rs2070744 (T-786C) of the eNOS gene and the rs5443 (C825T) of the GNB3 gene using the PCR-RFLP method. RESULTS: A significant association of the eNOS G894T (p = 0.005) and T-786C (p = 0.02) with altered susceptibility to VED was observed. The risk also holds for the G894T and T-786C eNOS gene polymorphisms when excluding patients with dyslipidemia and cardiovascular diseases (p = 1.7·10-4 and p = 3.2·10-5 , respectively). The univariate odds ratio associated with CC alleles of the eNOS T-786C revealed a four times increased risk for VED (OR = 4.04; 95% CI = 1.53-10.67; p = 0.006). VED risk was also associated with the G894T variant under dominant model (p = 0.002) and the T-786C variant under recessive model (p = 0.004). Furthermore, the concomitant presence of the combined genotypes of the 894T and 786T strongly affected the predisposition to VED (p = 0.007). DISCUSSION AND CONCLUSION: Our study gave a comprehensive insight into functional interaction between GNB3 and eNOS gene polymorphisms and suggests that the eNOS G894T and T-786C variants are strong predisposing factors of VED susceptibility within men with type 2 diabetes.

Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms.

Cluster headache is a disorder with increased hereditary risk. Associations between cluster headache and polymorphism rs2653349 of the HCRTR2 gene have been demonstrated. The less common allele (A) seems to reduce disease susceptibility. The polymorphism rs5443 of the GNB3 gene positively influences triptan treatment response. Carriers of the mutated T allele are more likely to respond positively compared to C:C homozygotes, when treated with triptans. DNA was extracted from buccal swabs obtained from 636 non-related Southeastern European Caucasian individuals and was analyzed by real-time PCR. Gene distribution for the rs2653349 was G:G = 79.1%, G:A = 19.2%, and A:A = 1.7%. The frequency of the wild-type G allele was 88.7%. The frequencies for rs5443 were C:C = 44.0%, C:T = 42.6%, and T:T = 13.4%. The frequency of the wild-type C allele was 65.3%. The frequency distribution of rs2653349 in the Southeastern European Caucasian population differs significantly when compared with other European and East Asian populations, and the frequency distribution of rs5443 showed a statistically significant difference between Southeastern European Caucasian and African, South Asian, and East Asian populations. For rs2653349, a marginal statistically significant difference between genders was found (p = 0.080) for A:A versus G:G and G:A genotypes (OR = 2.78), indicating a higher representation of male homozygotes for the protective mutant A:A allele than female. No statistically significant difference was observed between genders for rs5443. Cluster headache pathophysiology and pharmacotherapy response may be affected by genetic factors, indicating the significant role of genotyping in the overall treatment effectiveness of cluster headaches.

The genetic variant C825T of the beta 3 subunit of G protein is associated with hypertension in a Portuguese population. / A variante genética c825t da subunidade ß3da proteína G associa­se com a hipertensão arterial numa população portuguesa.

INTRODUCTION: Hypertension is an important public health problem, affecting about 25% of the adult population worldwide.1 Genetic and environmental factors contribute to its pathogenesis. The T allele of the C825T polymorphism of the beta 3 subunit of G protein (rs5443) leads to the production of a truncated variant that enhances intracellular signaling and may interfere with the regulation of blood pressure. This genetic variant has been described as a risk factor for hypertension, although study results are controversial. OBJECTIVE: The objective of this study was to analyze the association of the C825T polymorphism of the GNB3 gene with the occurrence of hypertension in a Portuguese population from the Madeira archipelago. METHODS: A case-control study was performed with 1641 Caucasian individuals (mean age 50.6±8.1 years), 848 with hypertension and 793 controls. Blood was collected from all participants for biochemical and genetic analysis, including genotyping of the C825T polymorphism. Logistic regression analysis was performed to determine which variables were significantly associated with the onset of hypertension. Statistical analyses were performed using IBM SPSS version 19.0 and p-values <0.05 were considered statistically significant. RESULTS: In our study, there was a significant association between the C825T polymorphism of the GNB3 gene and the occurrence of hypertension (odds ratio 1.275; 95% confidence interval 1.042-1.559; p=0.018) in the dominant model, after multivariate analysis. CONCLUSION: We conclude that the C825T polymorphism of the beta 3 subunit of G protein is significantly and independently associated with the occurrence of hypertension in the study population.

Association of G-Protein ß3 Subunit C825T Polymorphism with Seasonal Variations in Mood and Behavior.

OBJECTIVE: Seasonal affective disorder and seasonal changes in mood and behavior are associated with several genes that regulate circadian rhythms. In this study, we investigated the relationship between the C825T polymorphism of the G-protein ß3 subunit and seasonal variations in mood and behavior in a young healthy Korean population. METHODS: A total of 507 young Korean participants were recruited through a newspaper advertisement, and their seasonality was evaluated by the Korean version of the Seasonal Pattern Assessment Questionnaire to assess the global seasonality score (GSS). We analyzed the CC, CT, and TT genotypes and their association with the GSS score and subscales. RESULTS: T allele carriers of the GNB3 C825T polymorphism were more likely to score higher on body weight and GSS. In the female group, the T allele carriers obtained significantly high total GSS and its subscale scores for mood, body weight, energy level, and appetite; however, differences in genotypes and allele carriers were also observed in the male participants. CONCLUSION: These results suggested that GNB3 C825T polymorphism plays a role in seasonal variations in mood, body weight, energy level, and appetite in a Korean population, particularly in females.

[Single nucleotide polymorphisms of the CYP11B2, GNB3 and NOS3 genes in various ethnic groups of arctic zone of yakutia suffering from arterial hypertension].

OBJECTIVE: Introduction: This article presents the results of a study of the frequencies of single nucleotide polymorphisms of the CYP11B2 -344 T> C genes; GNB3 825 C> T; NOS3 -786 T> C and 894 G> T in different ethnic groups of residents of the Arctic zone of the republic "Sakha" (Yakutia), suffering from essential arterial hypertension. The aim: The aim of this study is to determine the presence of statistically significant differences in the frequencies of the above-mentioned polymorphisms in the studied ethnic groups of people living in the Arctic zone of Yakutia. PATIENTS AND METHODS: Materials and methods: The material for the study was whole blood obtained during venipuncture. The volunteer groups studied were formed along ethnic lines and included the Yakuts, Slavs, Evens, and Evenks. Further, the representatives of the aforementioned ethnic groups were further grouped by aboriginal basis, in accordance with which the following groups were formed: "Indigenous Minorities of the Arctic Zone" and "Non-Indigenous Ethnic Groups of the Arctic Zone". To identify the polymorphisms indicated above, the method of real-time polymerase chain reaction with detection of the melting point of duplexes was used. RESULTS: Results: As a result, statistically significant (p ≤ 0.05) differences between the considered, in the framework of this study, ethnic groups at the points CYP11B2 -344 T> C; NOS3 -786 T> C and 894 G> T. CONCLUSION: Conclusions: The revealed differences can be further considered as a basis for studying the clinical features of the course of arterial hypertension in people with polymorphisms of the respective genes, as well as a basis for further pharmacogenetic studies.

Association of G-Protein β3 Subunit C825T Polymorphism with Seasonal Variations in Mood and Behavior

OBJECTIVE: Seasonal affective disorder and seasonal changes in mood and behavior are associated with several genes that regulate circadian rhythms. In this study, we investigated the relationship between the C825T polymorphism of the G-protein β3 subunit and seasonal variations in mood and behavior in a young healthy Korean population. METHODS: A total of 507 young Korean participants were recruited through a newspaper advertisement, and their seasonality was evaluated by the Korean version of the Seasonal Pattern Assessment Questionnaire to assess the global seasonality score (GSS). We analyzed the CC, CT, and TT genotypes and their association with the GSS score and subscales. RESULTS: T allele carriers of the GNB3 C825T polymorphism were more likely to score higher on body weight and GSS. In the female group, the T allele carriers obtained significantly high total GSS and its subscale scores for mood, body weight, energy level, and appetite; however, differences in genotypes and allele carriers were also observed in the male participants. CONCLUSION: These results suggested that GNB3 C825T polymorphism plays a role in seasonal variations in mood, body weight, energy level, and appetite in a Korean population, particularly in females.

Genetic association analysis of serotonin and signal transduction pathways in suicide attempters from an Italian sample of psychiatric patients.

Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments. Genomic DNA was isolated from peripheral white blood cell samples and polymorphisms were genotyped by pyrosequencing technology. Although no differences were observed between allele and genotype frequencies for all polymorphisms and suicide attempt (SA), a polygenic risk score was detected for three genes HTR2A (A-1438G), TPH1 and TPH2 increasing the prediction of SA risk (Thresh=0.43, p=0.038, R2=0.053). Moreover some nominal associations were obtained after gender and phenotypic dissection stratification (TEMPS-A, TEMPs-H, GSMD, SHSS, GAF, CGI) for SLC6A4 (5-HTTLPR), HTR1A (C-1019G), HTR2A (A-1438G), TPH1 (A799C) and GNB3 (C825T) genes, that were lost after Bonferroni correction. This is a first evidence that specific additive combinations of genes could increase the prediction of SA risk and that gender and phenotypic dissection could influence the association of the genes with SA. This could represent a further study also for future meta-analyses on larger samples.

Mutation in the beta3 subunit of Guanine nucleotide-binding protein (GNB3) gene is not associated with Type II diabetes mellitus risk: a case-control study of a North Indian population.

CONTEXT: Genetics play a major role in development and pathophysiology of Type 2 diabetes mellitus (T2DM). OBJECTIVE: To asses the association of Guanine nucleotide-binding protein (GNB3) (C825T) gene's polymorphism with T2DM. MATERIALS AND METHODS: A case-control study including 400 North Indians was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) approach to analyze genetic polymorphism. RESULTS: No significant difference was observed in genotype and allele frequencies of GNB3 gene on comparing cases with controls. DISCUSSION: Our study is in agreement with studies on Polish, Japanese, Hispanic-American and Danish populations who observed no significant association between GNB3 (C825T) polymorphism and T2DM. CONCLUSION: GNB3 (C825T) polymorphism is not associated with T2DM.