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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.