C825T Polymorphism Of GNB3 Gene Research Articles

OS 05-02 ASSOCIATION OF G-PROTEIN BETA3 SUBUNIT GENE C825T POLYMORPHISM WITH CARDIAC AND CEREBROVASCULAR EVENTS IN CHINESE HYPERTENSIVE PATIENTS

Objective: Several recent studies showed C825T polymorphism is related to cardiac and cerebrovascular diseases (CCVD) in normal population. However, studies on whether 825T allele influences the incidence of CCVD in hypertensive population are rare. Design and Method: 695 patients with essential hypertension were genotyped for C825T polymorphism of GNB3 gene and followed 8 years for major adverse cardiac and cerebrovascular events (MACCEs). Established cardiac and cerebrovascular risk factors were used to adjust the multivariate Cox analysis. Results: After a mean follow-up period of 7.60 ± 1.12 years, a significantly higher incidence of MACCEs was seen in TT genotype group than CC and CT genotypes. The TT variant was significantly and independently predictive of MACCEs (relative risk = 2.579; p < 0.001), CVD (relative risk = 2.983; p < 0.001), but not stroke, CVD + stroke or death. Conclusions: The GNB3 TT genotype is a risk factor for CVD independent of other established cardiovascular risk factors in Chinese hypertensive patients.

The C825T GNB3 polymorphism, independent of blood pressure, predicts cerebrovascular risk at a population level

The role of C825T polymorphism of the candidate GNB3 gene in predicting cerebrovascular outcome has been poorly explored in longitudinal setting at a population level. In an epidemiological setting, 1,678 men and women from general population were genotyped for C825T polymorphism of GNB3 gene and follow-up for 10 years to detect nonfatal and fatal cerebrovascular events (CE). Established cerebrovascular risk factors were used to adjust the multivariate Cox analysis for confounders. Seventy-three nonfatal and 30 fatal CE were recorded. Incidence of CE was higher in TT than in C-carriers (fatal: 2.6 vs. 1.7%, P < 0.03; nonfatal: 7.8 vs. 3.9%, P < 0.03; fatal recurrences: 1.6 vs. 0.6%, P < 0.03). In Cox analysis, the TT genotype predicted nonfatal (hazard ratio 1.99, 95% confidence interval 1.05-3.79, P = 0.03), fatal (2.91, 1.05-8.12, P = 0.04), and fatal recurrent CE (6.82, 1.50-31.1, P = 0.02) also after adjustment for age, gender, systolic and diastolic blood pressure, body adiposity, atherogenetic blood lipids, serum uric acid, diabetes, calories, caffeine and ethanol intake, and coronary events at baseline. Further adjustment for historical CE made the association between TT genotype and incident fatal CE nonsignificant (hazard ratio 2.72, 95% confidence interval 0.96-7.22, P = 0.06). The TT genotype of GNB3 gene predicts incident CE independent of blood pressure and other established risk factors at a population level. Further studies are needed to clarify the nature and pathways of this association.

48 Polymorphisms In α‐Adducin (G460w) and G‐Protein β‐3 Subunit (C825t) Genes In Essential Hypertension

Objectives Essential hypertension (EH) has a multifactorial origin and is thought to arise from an interaction between susceptibility genes and environmental factors. A number of candidate genes have been proposed. In our study, the role of polymorphisms in α‐adducin (ADD1) and G‐protein β‐3 subunit (GNB3) genes in EH was investigated.Design and Methods Ninety‐three children and young adults, aged from 4 to 27 years, with both parents, were included in our study, giving 93 nuclear families. Two polymorphisms were detected using the polymerase chain reaction technique (PCR). Investigating the C825T polymorphism of GNB3 the C allele was identified by the presence of 152 and 116 bp signals and the T allele was present when a non‐digested 268 bp long band was detected. The allele‐specific polymerase chain reaction (PCR) was used to study the G460W polymorphism of ADD1. For statistical analysis the transmission disequilibrium test (TDT) was used. By using non‐transmitted alleles as the control population, problems of population admixture and mismatched controls are avoided.Results The following genotype frequencies for G460W polymorphism in ADD1gene were observed: 67 (72.0%) were GG homozygotes, 23 (24.7%) were GW heterozygotes and 3 (3.3%) were WW homozygotes. Using the TDT test, 44 nuclear families were used. There were 63 transmitted G alleles, 25 transmitted W alleles, 60 non‐transmitted G alleles and 28 non‐transmitted W alleles. The observed difference was not statistically significant (χ2 = 0.24, P = 0.62).The following genotype frequencies for the C825T polymorphism in GNB3 gene were found: 50 (53.8%) were CC homozygotes, 35 (37.6%) were CT heterozygotes and 8 (8.6%) were TT homozygotes. 73 nuclear families were used. There were 95 transmitted C alleles, 51 transmitted T alleles, 84 non‐transmitted C alleles and 62 non‐transmitted T alleles. The observed difference again was not statistically significant (χ2 = 1.75, P = 0.19).Conclusions Our study found no association of the polymorphisms in ADD1 and GNB3 genes with EH, respectively. However, our sample size was rather small. It seems very likely that many genes with small effects (such as the gene variants above) account for the heritability of EH.