G-protein Β3 Subunit C825T Polymorphism Research Articles

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.

Association of G-protein β3 subunit C825T polymorphism with essential hypertension: evidence from 63 729 subjects.

Many studies have reported that G-protein β3 subunit (GNB3) C825T polymorphism is associated with essential hypertension (EH), although this remains subject to debate. Thus, meta-analysis was carried out to clarify this relationship. A total of 75 articles, reporting 81 case-control studies evaluating 28 369 patients and 34 933 control individuals, were assessed. Overall, a significant association was observed in the dominant model (odds ratio (OR)=1.11, 95% CI 1.04-1.19), recessive model (OR=1.09, 95% CI 1.01-1.17), TT vs CC (OR=1.16, 95% CI 1.05-1.28), CT vs CC (OR=1.09, 95% CI 1.02-1.17), and additive model (OR=1.07, 95% CI 1.02-1.13) after pooling all eligible studies. Subgroup analysis by ethnicity and gender demonstrated significantly increased EH only in Caucasians using the dominant (OR=1.22, 95% CI 1.07-1.39; TT vs CC, OR=1.29, 95% CI 1.07-1.54; CT vs CC, OR=1.19, 95% CI 1.05-1.35) and additive (OR=1.16, 95% CI 1.05-1.28) models. In summary, the present meta-analysis indicated the GNB3 C825T polymorphism is related to increased EH exclusively in Caucasians.

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case-control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74-1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89-1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86-1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75-1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05-2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population.

Association Study of the G-Protein β3 Subunit C825T Polymorphism with Disease Progression an Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma

The T-allele of a common C825T single nucleotide polymorphism (SNP) in the gene GNB3, encoding the G3 subunit of heterotrimeric G-proteins, is associated with a truncated form of the G3 protein that imparts a greater signaling capacity than the alternative C-allele encoding a nontruncated protein. We analyzed the C825T-allele status with regard to disease progression in patients with head and neck squamous cell carcinoma (HNSCC). The prognostic value of the SNP was evaluated in an unselected series of 341 patients treated with curative intent for HNSCC including all tumor stages with different therapeutic regimens. Genotype analysis was done by Pyrosequencing using DNA from paraffin-embedded tissue samples. Genotypes were correlated with relapse-free and overall survival. Proportions of 5-year relapse-free intervals were 62% for CC, 60% for TC, and 42% for TT genotypes. Kaplan-Meier curves revealed a significant genotype-dependent relapse-free interval (P = 0.036). In multivariate analysis with stage, localization, grade, gender, and smoking habits as covariates, GNB3 825T homozygous patients displayed a higher risk for relapse than C825 homozygous patients (TT versus CC, hazard ratio; 95% confidence interval, 1.4-4.8; P = 0.002). The same genotype effect was found for overall survival, TT genotypes were at higher risk for death compared with CC genotypes (hazard ratio, 2.6; 95% confidence interval, 1.6-4.3; P < 0.001), and 5-year survival proportions were 60% for CC, 52% for TC, and 33% for TT. The GNB3 C825T SNP thus represents a host derived prognostic marker in HNSCC, which allows identifying high-risk patients, which could benefit from novel and/or more aggressive therapeutic regimes.

Possible association between G-protein β3 subunit C825T polymorphism and antipsychotic-induced restless legs syndrome in schizophrenia.

The incidence of restless legs syndrome (RLS) is presumed to be higher among people with schizophrenia who take antipsychotic medication, most of which blocks the dopamine D2 receptor. The purpose of this study was to determine whether the G-protein β3 subunit (GNB3) C825T polymorphism is associated with antipsychotic-induced RLS in schizophrenia. We examined 178 Korean patients with schizophrenia. All of the subjects were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group and the International Restless Legs Scale. Genotyping was performed for the C825T polymorphism in the GNB3 gene. The genotype distribution did not differ significantly between antipsychotic-induced RLS patients and patients who had no-RLS symptoms (χ 2 = 4.30, p = 0.116). The genotypes of the C825T single-nucleotide polymorphism (SNP) were classified into two groups: C+ (CC and CT genotypes) and C- (TT genotype). The presence of the C allele (C+) was associated with an increased likelihood of RLS (χ 2 = 4.14, p = 0.042; odds ratio = 2.56, 95% confidence interval = 1.02-6.47). These results suggest that the GNB3 C825T SNP is associated with RLS in schizophrenia. However, confirming this association requires future larger scale studies in which the effects of medication are strictly controlled.

Association study of the G-protein β3 subunit C825T polymorphism with disease progression in patients with bladder cancer

The T-allele in the GNB3 C825T polymorphism has been associated with increased cell migration, a prerequisite for metastasis. In this study we investigated a potential association of the C825T-allele status and disease progression in patients with transitional cell carcinoma of the bladder (TCC). Genotyping of the GNB3 C825T polymorphism was performed in 389 patients with transitional cell carcinoma of the bladder and in 104 control subjects and clinical follow-up was worked up in 339 patients. Genotype distribution in 389 patients with bladder cancer was comparable to genotype distribution of the control group. There was no association of GNB3 C825T genotype with tumor stage or grade, but follow-up analysis in the subgroup of non-smokers revealed a shorter time to metastasis in 825T-allele carriers compared to individuals homozygous CC. The genotype of the GNB3 C825T polymorphism appears to influence the biological behavior of tumor disease in non-smoking TCC patients.

G-Protein β3 Subunit C825T Polymorphism Tends to Be Associated with Seasonal Variation in Young Male College Students

This study investigated the relationship between G-protein β₃ subunit (GNB3) C825T polymorphism and seasonal variation in 189 young male college students. The subjects were genotyped for C825T and were evaluated by the Seasonality Pattern Assessment Questionnaire. The Global Seasonality Score (GSS) between the three genotypes revealed a marginal difference. The heterozygotes showed significantly higher seasonal variations in GSS than the homozygotes. The prevalence of heterozygotes tended to be higher in seasonals compared with normal subjects, although it was not statistically significant. These results suggest that GNB3 C825T polymorphism tends to be related to seasonal variation in mood and behavior in the normal population.

Frequencies of the G-protein β3 subunit C825T polymorphism and the δ 32 mutation of the chemokine receptor-5 in patients with multiple sclerosis

In the pathogenesis of multiple sclerosis (MS) genetic factors are known to influence autoreactive T-cell-actions like proliferation and chemotaxis across the blood–brain barrier via chemokine receptors (CCR) and G-protein coupled activating mechanisms. For the first time, we studied the frequencies of a recently described C825T polymorphism in the G-protein encoding gene for the β3 subunit (GNB3) together with frequencies of a 32-base-pair deletion in the CCR5 gene (δ32 CCR5) in patients with MS ( n=253: relapsing-remitting (RR), n=124 and chronic progressive course, n=129). Apart from a trend to a reduced frequency of δ32 CCR5 and increased GNB3 825T polymorphism in primary chronic progressive patients, numbers did not reach statistical significance in any group of MS. These results could not support differences in the genetic background of MS based on that CCR5 mutation or the described GNB3 polymorphism.

G-protein β3-subunit gene variant, blood pressure and erythrocyte sodium/lithium countertransport in essential hypertension

Recently, a C825T polymorphism in the gene coding for the β3 subunit of G proteins (GNB3) has been described in cells from patients with essential hypertension and enhanced Na+/H+ exchange activity. This study aims to evaluate the association between the 825T allele and activity of erythrocyte sodium/lithium countertransport (Na+/Li+ CT) and other sodium transport systems in red blood cells from patients with essential hypertension. A group of 77 patients (36 male, 41 female; aged 51.7 ± 1.1 years) was studied. The maximal rates (Vmax) of Na+/Li+ CT, Na+/K+/Cl-cotransport and Na+K+ ATPase were evaluated in erythrocytes from all the patients. They were genotyped for the C825T polymorphism by a polymerase chain reaction (PCR) method, followed by digestion with BseDI. Body mass index (BMI) was higher in CT+TT patients than in CC patients (28.9 ± 0.5 vs. 27.0 ± 0.7 kg/m2; P=0.023). Hypertensives with the T allele (CT+TT genotypes) showed significantly higher systolic blood pressure (BP) values (156.9 ± 2.1 vs. 148.9 ± 2.8 mmHg; P=0.024), whereas differences in diastolic BP did not reach statistical significance (96.4 ± 1.0 vs. 94.0 ± 1.1 mmHg; P=0.120). No differences in the Vmax of Na+/Li+ CT between the genotypes was seen (CC: 236 ± 19 and CT+TT 277 ± 23 mmol/L cells per h; P=0.221). Similarly, no differences were detected in the Vmax of erythrocyte Na+/K+/Cl-cotransport and Na+K+ ATPase among the genotypes. There was no appreciable association between the G-protein β3-subunit C825T polymorphism and erythrocyte Na+/Li+ CT and other sodium transport systems in the hypertensive patient sample studied; however, those with the T allele were more obese and had more severe systolic hypertension.

G-protein beta3 subunit C825T polymorphism: no association with risk for hypertension and obesity.

Several recent studies have indicated that a C825T polymorphism in the gene encoding the G-protein beta3 subunit is a significant risk factor for hypertension and obesity. In this study, we tested whether this polymorphism is associated with hypertension and obesity in white men. Population-based prospective cohort study. We followed a cohort of 903 men, aged 42-61 years at baseline, for an average time of 4.2 years. Genotyping was performed by polymerase chain reaction. The genotype distribution was in Hardy-Weinberg equilibrium: 514 (57%) had the CC genotype, 49 (5%) had the TT genotype and 340 (38%) were heterozygous (T:C = 0.24:0.76). There was no statistically significant difference between the genotype groups in respect to baseline and end of follow-up risk for hypertension or obesity, systolic or diastolic blood pressure, or body mass index. We conclude that the C825T polymorphism of the G-protein beta3 subunit gene does not notably contribute to the development of hypertension or obesity, and is not a significant determinant for blood pressure and body mass index in white men.

The human G-protein beta3 subunit C825T polymorphism is associated with coronary artery vasoconstriction.

Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein beta3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein beta3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans. We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. The C825T polymorphism of the G-protein beta3 subunit may be a genetic determinant of coronary artery vasomotion in humans.