GNB3基因C825T多态性与新疆和田地区维吾尔族自然长寿老人的相关性研究

目的 探讨GNB3基因C825T多态性与新疆和田地区维吾尔族老人长寿的关系.方法 采用聚合酶链反应-限制性片段长度多态法(PCR-RFLP)和直接测序法检测百岁组(年龄不小于100岁)65例和长寿组(90-99岁)100例老人GNB3基因825位点的基因型,对照组112例(年龄不超过70岁自然死亡人群)作为对照组.结果 百岁组和对照组GNB3 825C/T的基因型和等位基因频率分布差异均具有统计学意义(P=0.0021,P<0.0001).其中百岁组CC基因型的频率为60.0%,对照组为36.6%(OR 2.60;95%CI 1.39-4.89).结论 本研究初步表明,新疆和田地区维吾尔族人GNB3基因C825T多态性与个体寿命密切相关,但同时也应考虑长寿是年龄依赖的多种因素影响的结果.     

GNB3基因C825T多态性与中国高血压患者服用坎地沙坦酯或坎地沙坦酯／氢氯噻嗪复方制剂降压疗效的相关性研究

目的探讨GNB3C825T基因多态性与坎地沙坦酯及复方坎地沙坦酯（坎地沙坦酯＋氢氯噻嗪）降压疗效的相关性。方法62名原发性高血压患者随机分组，分别给予坎地沙坦酯片及坎地沙坦酯＋氢氯噻嗪片治疗8周，定期随访取得血压下降数据。采用聚合酶链式反应．限制性片断长度多态性（PCR-RFLP）方法检测GNB3基因型。利用协方差分析各基因型与两药物降压疗效的关系。结果服用坎地沙坦酯／氢氯噻嗪复方的病人血压下降值明显高于单独服用坎地沙坦酯的病人血压下降值（P〈0．05）。GNB3825T等位基因在入选的高血压病人中频率为45．16％。与多数国人报道结果一致。协方差分析结果显示服用两种药后收缩压和舒张压的下降幅度在GNB3C825T各基因型高血压患者问比较均无统计学差异（P〉0．05）。结论GNB3C825T基因多态性可能与坎地沙坦酯及坎地沙坦酯＋氢氯噻嗪降压疗效不相关。     

Lack of an Association of GNB3 C825T Polymorphism and Blood Pressure in Patients with Rheumatoid Arthritis

G-protein beta 3 subunit (GNB3) C825T (rs5443) single nucleotide polymorphism (SNP) has been implicated as a risk factor for essential hypertension in the general population. The effects of this SNP may be more prominent in subjects with endothelial dysfunction (ED). Rheumatoid arthritis (RA) is associated with ED and has a high prevalence of hypertension. Thus far, this SNP has not been studied in RA patients. We genotyped 383 RA patients and 432 controls. GNB3 C825T was identified using real-time polymerase chain reaction (PCR) and melting curve analysis. There were no differences in the frequencies of the GNB3 C825T genotype and alleles between RA and controls. Within RA patients, prevalence of hypertension did not differ across genotypes. The TT versus CC+CT contrast yielded an adjusted odds ratio (OR) of 0.92 (95% CI: 0.49 to 1.76, p = 0.813), the contrast of TT+CT versus CC an adjusted OR of 2.17 (95% CI: 0.885 to 5.30, p = 0.091), whereas that of the T allele versus C allele an adjusted OR of 1.11 (95% CI: 0.76 to 1.61, p = 0.604). Systolic and diastolic blood pressure levels were not significantly different across the three genotypic groups. No significant interaction was observed between GNB3 825C/T polymorphism and serum endothelin levels. Data from the present study suggest that the T825 variant of the G protein β3 subunit gene is unlikely to constitute major susceptibility loci for essential hypertension in Caucasian RA patients. Further larger studies are required to confirm our findings and assess the interaction of rs5443 with environmental factors.     

G Protein Beta3 Subunit Variant: Tendency of Increasing Susceptibility to Hypertension in Japanese

The mechanism of human G beta mutation, G beta3-s, to produce a "gain-of-function" G-protein signaling abnormality remains to be elucidated. Both the enhanced Gi-mediated signalings and the expression of G beta3-s have been demonstrated to be associated with hypertension, together with the finding that the T825 variant might be associated with the occurrence of a splice variant GNB3-s in a white population. The aim of the present study was to reveal a key role of G beta by confirming the association between this polymorphism and susceptibility of hypertension in Japanese. Genotype analysis of 180 normotensive and 179 hypertensive subjects suggests that the T allele tends to be related to the prevalence of hypertension. When age, sex and body mass index were controlled by multiple logistic regression, odds ratios for hypertension associated with the T allele were 1.77 (TT vs CC; 95% confidence interval (CI) 0.97-3.21; p = 0.06), 1.13 (TC vs CC; 95% CI 0.62-2.05; p = 0.69) and 1.40 (TT + TC vs CC; 95% CI 0.81-2.40; p = 0.23). The T allele frequency was found to be significantly higher in hypertensives than in normotensives (0.63 vs 0.56; ≤2 = 4.27; p = 0.04), both of which are considerably higher than the frequency observed in Whites. Higher T allele frequencies in Japanese may represent one of the ethnic differences: a larger subgroup whose hypertension is increased by excessive salt diet. Confirming the association between the T allele and hypertension by further investigation and then utilizing the various intermediate features or phenotypes, such as Na + /H + exchanger activity and renin levels, may help to unravel the active role of the beta subunit.     

Association of G-protein beta3 subunit gene C825T polymorphism with cardiac and cerebrovascular events in Chinese hypertensive patients

Several recent studies showed that C825T polymorphism is related to cardiovascular diseases in normal population. However, studies on whether 825T allele influences the incidence of cardiovascular diseases in hypertensive patients are rare. In the current study, 729 patients (CC, n = 332; CT, n = 313; TT, n = 84) with essential hypertension were genotyped for C825T polymorphism of the GNB3 gene and followed 8 years for major adverse cardiovascular events (MACEs) which include stroke, the onset of coronary artery disease (CAD), and all-cause death. Established cardiovascular risk factors were used to adjust the multivariate Cox analysis. After a mean follow-up period of 7.60 ± 1.12 years, a significantly higher incidence of MACEs was seen in the TT genotype group than CC and CT genotypes. The TT variant was significantly and independently predictive of MACEs (relative risk = 2.574; p < 0.001), CAD (relative risk = 2.963; p < 0.001), but not stroke, CAD+stroke or death. The GNB3 TT genotype is a risk factor for CAD independent of other established cardiovascular risk factors in Chinese hypertensive patients.     

Association of insulin sensitivity and glucose tolerance with the c.825C>T variant of the G protein beta-3 subunit gene

The risk of macrovascular complications of diabetes mellitus is greatly enhanced by the presence of high blood pressure. In addition, hypertension and diabetes share insulin resistance as a common pathophysiological mechanism. Despite evidence for a common molecular genetic background of insulin resistance, glucose intolerance, and hypertension, few candidate genes have been shown to influence all of these features simultaneously. We examined the association of insulin sensitivity with the c.825C>T variant of the g-protein beta-3 subunit (GNB3), a candidate gene of hypertension, in families of Mexican-American hypertensive patients.

Methods

One hundred eighty subjects enrolled in a family study of Mexican-American hypertensive patients were recruited from hypertension clinics in Los Angeles. Subjects underwent pretreatment blood pressure recording, an oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and anthropometric measurements. DNA from peripheral blood leukocytes was genotyped by polymerase chain reaction and restriction enzyme digest with BseD1 (GNB). Statistical analysis was performed by transmission disequilibrium testing.

Results

In carriers of the T-allele, blood glucose was significantly lower [(mean+S.D.) fasting: 96.7+22.9 vs. 106.7+51.7mg/dl, P=.009; oral glucose tolerance test (oGTT) 120 min: 131.7+48.7 vs. 137.8+64.9 mg/dl, P=.036], and insulin sensitivity was significantly higher (229.0+108.7 vs. 188.5+94.2 mg/kg per minute, P=.037) than in homozygous carriers of the C-allele. Blood pressure did not differ significantly between the phenotypes.

Conclusion

In a Mexican-American hypertensive population, we found evidence for higher insulin sensitivity in carriers of the T allele of the c.825C>T variant of GNB3.     

GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study

Objective

The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level.

Methods

In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders.

Results

The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p < 0.001).

Conclusion

The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.     

温州地区汉族人群G蛋白β3亚基C825T基因多态性与肥胖的相关性研究

目的研究温州地区汉族人群G蛋白β3亚基（GNB3）C825T等位基因多态性与超重及单纯性肥胖的相关性。方法超重及单纯性肥胖组为肥胖专科门诊中随机选取161例超重或单纯性肥胖患者，并于温州市中心血站随机选取313名体重正常健康献血者为对照组，PCR-RFLP检测基因型。结果（1）温州地区汉族人群GNB3 825T等位基因频率为0．428，与其他人种的基因频率显著不同。（2）超重及单纯性肥胖组的TT基因型携带者显著增加（P〈0．01），TT／CT导致肥胖的比数比（OR值）为2．9（95％可信区间1．8-4．7，P〈0．01）；TT／CC致肥胖的OR值为2．7（95％CI 1．5—4．7，P〈0．01）；TT基因型分布按体重指数（BMI，kg／m^2）分组后，正常体重（18≤BMI〈23）、超重（23≤BMI〈25）、Ⅰ度肥胖（25≤BMI〈30）和Ⅱ度肥胖（BMI≥30）4组均显著高于低体重（BMI〈18组，P〈0．05或P〈0．01）；Ⅰ度肥胖、Ⅱ度肥胖组高于正常体重组（均P〈0．05）；Ⅱ度肥胖组高于超重组（P〈0．01）。（3）同组男女间比较GNB3 C825T基因型和T等位基因频率分布差别无统计学意义。结论GNB3 C825T等位基因频率分布存在种族差异，温州地区汉族人群GNB3 825T等位基因频率为0．428，GNB3 825T等位基因与超重及单纯性肥胖呈正相关。GNB3 825T基因型可作为早期预测单纯性肥胖的遗传学指标之一。     

The C825T polymorphism in the human G-protein β3 subunit gene is not associated with diabetic nephropathy in Type I diabetes mellitus

Summary In Type I (insulin-dependent) diabetes mellitus a genetic predisposition exists to nephropathy and is related to parental hypertension. Enhanced G-protein activation, a cellular phenotype observed in cultured cells from patients with essential hypertension, was recently documented in Type I diabetic subjects with nephropathy. This enhanced G-protein activation has been associated with a genetic variant in the G-protein β3 subunit, GNB3. A C→T polymorphism at position 825 in exon 10 is associated with G-protein activation, the T allele associated with enhanced activity. Furthermore the T allele was observed more frequently in a group with essential hypertension. In this report we have analysed the role of the C825T polymorphism in the predisposition to diabetic nephropathy in Type I diabetes. We have investigated the frequency of this polymorphism in a large case-control study and found no association of the T allele with diabetic nephropathy. Specifically carriage of the T allele as CT or TT was observed in 49 % of 200 Type I diabetic control subjects with normoalbuminuria (diabetes duration 24 years) compared with 53 % of 216 Type I diabetic subjects with nephropathy (overt proteinuria or end-stage renal failure). Within this group we have also examined the inheritance of C825T alleles in a family study and found no evidence for excess transmission of the T allele to Type I diabetic offspring with nephropathy (T allele transmitted to 51 % of nephropathy offspring, C allele transmitted to 49 % of nephropathy offspring, p = 0.79). In none of the Type I diabetic datasets examined was there any effect of genotype on variation in systolic or diastolic blood pressure. In conclusion we can find no evidence for the C825T polymorphism of the β3 G-protein subunit as a major gene in the susceptibility to diabetic nephropathy in Type I diabetes. [Diabetologia (1998) 41: 1304–1308] Received: 27 April 1998 and in revised form: 9 July 1998     

Interaction of the ACE D allele and the GNB3 825T allele in myocardial infarction

In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 825T allele of the G-protein ss(3)-subunit gene (GNB3) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D:/I variant affects the renin-angiotensin system hormones that activate G-protein-coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D: allele and the GNB3 825T allele (P<0.001). The odds ratio for MI, associated with the 825T allele, was not increased in the presence of the ACE II genotype (OR 0.5; P=0.09) but was significantly higher in 825T allele carriers with the ACE DI genotype (OR 1.9; P=0.01) and further increased in individuals with the ACE DD genotype (OR 2.4; P=0.02). The highest odds ratio was found in homozygous 825T allele carriers with the ACE DD genotype (OR 7.5; P=0.006). Our data suggest a significant interaction of the GNB3 825T allele with the ACE D allele in MI. These hypothesis-generating data may justify larger prospective studies.     

C825T polymorphism of the GNB3 gene codifying the G-protein beta3-subunit and cardiovascular risk

Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure. A polymorphism (825C/T) in exon 10 of the GNB3 gene, that encodes for the beta3 subunit, has recently been described. The 825T allele is associated with alternative splicing of the gene and formation of a truncated but functionally active beta3 subunit. Carriers of the 825T allele appear to have an increased risk for hypertension, obesity, insulin-resistance and left ventricular hypertrophy. Moreover, 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic and with clonidine. GNB3 825T allele may be regarded as a potential genetic marker for a better definition of the risk profile of hypertensive subjects, but further studies are needed to precisely define the impact of T allele on the prognosis of such patients.     

G protein beta3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension.

BACKGROUND: A nucleotide substitution (C-->T) at position 825 of the gene GNB3 encoding the beta3 subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives. PROCEDURES: Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. RESULTS: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 +/- 1.5 v 89.7 +/- 1.5 g/m2; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity. CONCLUSIONS: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.     

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

Aims/hypothesis The 825C>T polymorphism in the gene encoding the G protein β3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome. Materials and methods The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case–control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects. Results We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007); however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels—a finding in contrast with most previous studies–but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant. Conclusions/interpretation The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.     

Association of the GNB3 825T-allele with better survival in patients with glioblastoma multiforme

Purpose

Genotypes of the C825T polymorphism of the GNB3 gene encoding the G protein β3 subunit were recently associated with the prognosis of different malignomas. We investigated potential associations of GNB3 genotypes with survival of patients with glioblastoma multiforme (GBM).

Methods

One hundred and sixty-one patients suffering from GBM were retrospectively investigated. Inclusion criteria were availability of DNA and a follow-up of at least 24 months. The results were evaluated with respect to the basic clinical data, type of surgical intervention, MGMT promoter methylation, adjuvant therapy, and survival.

Results

After 2 years of first diagnosis, 128 (79.5%) of the 161 patients had died, 33 (20.5%) were alive. Kaplan–Meier curves revealed a significant higher rate of survival for homo- and heterozygous T-allele carriers (P = 0.019) with 38.5 and 25.3%, respectively, but only 11.6% for homozygous C-allele carriers. Multivariable Cox regression identified the heterozygous (hazard ratio 3.3, 95% CI 1.3–8.0, P = 0.010), as well as homozygous GNB3 825 C-allele (hazard ratio 3.7, 95% CI 1.5–9.1, P = 0.004) as an independent negative prognostic factor for 2-year survival according to the GNB3 825 TT genotype reference group.

Conclusions

Our data suggest an association of the GNB3 825TT genotype and better survival in patients with GBM.     

G蛋白β3亚单位825T等位基因与2型糖尿病及其并发肾病的相关性研究

目的 研究G蛋白β3亚单位825T等位基因与2型糖尿病及糖尿病肾病的相关性。方法 在单纯2型糖尿病(77例)和并发糖尿病肾病(71例)的患者中采用PCR—RFLP方法研究G蛋白β：亚单位C825T基因多态性，以正常人及原发性高血压患者为对照。结果 单纯糖尿病人群T等位基因(46．1％)及TT基因型频率(20．8％)稍高于对照组(T等位基因频率40．4％，TT基因型频率14．6％)，但末达统计学显著意义，而糖尿病肾病组两种指标均明显高于对照组(P＜0．05)。结论 G蛋白β3亚单位825T等位基因与糖尿病肾病相关，可能是糖尿病发病的候选基因。     

小剂量奥美拉唑治疗功能性消化不良

背景:功能性消化不良(FD)在我国很常见。制酸剂对溃疡样消化不良有一定疗效,但尚有待进一步研究。目的:评估小剂量奥美拉唑对FD的疗效。方法:将160例FD患者随机分为两组,分别予奥美拉唑10 mg每日1次或西沙必利5 mg每日3次治疗,疗程2周。结果:治疗后,奥美拉唑组和西沙必利组的反酸、饱胀、上腹痛/不适症状积分和症状总积分均较治疗前下降。奥美拉唑组的反酸和上腹痛/不适症状积分下降比显著高于西沙必利组,症状总积分由治疗前的10.27±3.02下降至治疗后的4.84±3.49(P<0.01),下降值和下降比分别为5.43±3.89和52.9%±34.0%,均显著高于西沙必利组(3.61±3.93和34.4%±50.1%.P<0.01)。奥美拉唑组和西沙必利组症状缓解的总有效率分别为94.7％和81.8%(P<0.01)。结论:小剂量奥美拉唑对溃疡样消化不良较西沙必利有更好的疗效。     

825T allele of the G-protein beta3 subunit gene (GNB3) is associated with impaired left ventricular diastolic filling in essential hypertension.

OBJECTIVE: Recently, a novel C825T polymorphism in the gene (GNB3) encoding for the G-protein beta3 subunit was identified. The 825T allele is associated with the generation of a novel splice variant, enhanced intracellular signal transduction, and arterial hypertension. In this study, we investigated the impact of the 825T allele on left ventricular structure and function in mild to moderate essential hypertensive subjects. METHODS: In 34 white patients with established mild to moderate essential hypertension (World Health Organization stage I or II, mean age 52 +/- 9 years) genotype analysis of GNB3 C825T polymorphism, insertion/deletion polymorphism of the ACE gene and 1166 A/C polymorphism of the AT1 receptor gene was performed. In each patient, 24 h ambulatory blood pressure measurement (SpaceLabs 90207) and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. RESULTS: In our homogenous study group, the GNB3 825T allele was not associated with casual and 24 h ambulatory blood pressure (CC versus TC/TT: 144 +/- 13/92 +/- 8 versus 151 +/- 14/97 +/- 7 and 143 +/- 11/92 +/- 7 versus 150 +/- 16/ 96 +/- 9 mmHg, respectively) or parameters of left ventricular structure (relative wall thickness: CC versus TC/TT, 0.48 +/- 0.1 versus 0.46 +/- 0.1; left ventricular mass: CC versus TC/TT, 281 +/- 65 versus 299 +/- 80 g). However, transmitral flow variables reflecting left ventricular diastolic filling were impaired in patients expressing the TC/TT genotype (ratio of peak late (A) to early (E) velocities: CC versus TC/TT, 0.95 +/- 0.24 versus 1.2 +/- 0.26, P< 0.02; velocity time integrals A/E: CC versus TC/TT, 0.57 +/- 0.16 versus 0.76 +/- 0.23, P< 0.01) while all co-variables such as age, body mass index, ambulatory blood pressure, heart rate and end-diastolic volume were similar between the two groups. If patients were stratified according to the I/D polymorphism of the ACE gene and the A1166C polymorphism of the AT1 receptor gene, no differences in blood pressure, left ventricular structure or systolic and diastolic function of the left ventricle were found between different genotypes. CONCLUSION: The GNB3 825T allele was associated with impaired left ventricular diastolic filling in hypertensive subjects in this study. Since alterations in left ventricular filling have been identified as an early marker of hypertensive heart disease, the GNB3 C825T polymorphism may influence cardiac adaptation to increased afterload.     

The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14,094 cases and 17,760 controls

OBJECTIVES: The C825T single nucleotide polymorphism of the G-protein beta3 (GNB3) has been implicated in susceptibility to essential hypertension, through the expression of an alternatively spliced truncated variant. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based case-control genetic association studies. METHODS: Random-effects methods were applied on summary data in order to combine the results of the individual studies. RESULTS: We identified in total 34 studies, including 14,094 hypertensive cases and 17,760 controls. The TT versus CC + CT contrast yielded an overall odds ratio (OR) of 1.08 [95% confidence interval (CI): 1.01, 1.15], the contrast of TT + CT versus CC, an OR of 1.17 (95% CI: 1.06, 1.29), whereas that of the T allele versus C allele yielded a non-significant OR of 1.05 (95% CI: 0.98, 1.13). There was moderate evidence for a publication bias in the latter two contrasts, which was eliminated after excluding studies not in Hardy-Weinberg equilibrium and those performed on non-normal populations (those with a diagnosis of diabetes, obesity and myocardial infarction). Subgroup analyses revealed that non-significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, the frequency of the T allele was lower in Caucasians and these populations were found to inhabit higher latitudes. CONCLUSIONS: The findings are in agreement with a recently proposed causal model for systolic blood pressure, which correlates it with the T allele and the absolute latitude. Further studies are needed in order to fully address questions about the aetiological mechanism of the particular association, as well as to study the effect in populations of African descent.