Gender-Specific Association between Angiotensin II Type 2 Receptor −1332 A/G Gene Polymorphism and Advanced Carotid Atherosclerosis

Ana Kolaković, Aleksandra Stanković, Tamara Djurić, Maja Živković, Igor Končar, Lazar Davidović, Djordje Radak, Dragan Alavantić

The angiotensin II type 2 receptor (AT2R) -1332 A/G polymorphism has been denoted as functional and associated with certain cardiovascular disease phenotypes. However, there are no studies considering the association of this gene polymorphism with carotid atherosclerosis (CA) and cerebrovascular events. Therefore, the aim of our study was to investigate a possible association of the AT2R -1332 A/G polymorphism with the occurrence of carotid plaques (CPs) and history of cerebrovascular insult (CVI) in advanced CA. The study group included 381 controls and 509 patients with CA consecutively admitted for endarterectomy. Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association was analyzed separately for males and females because the AT2R gene is located on the X chromosome. The AT2R -1332 GG genotype was associated with the advanced CA in the female study group (recessive model of inheritance, AA+AG versus GG; adjusted odds ratio [OR] = 2.25; 95% confidence interval [CI] 1.17-4.33; P = .01). In the male subgroup of patients with CA, the significant overrepresentation of G/- hemizygote was detected in patients with CVI compared to male patients without this event (crude OR = 2.05, 95% CI 1.20-3.50, P = .008). This study suggests a gender-specific association between the AT2R -1332 A/G polymorphism and the occurrence of CP and the history of CVI in advanced CA, but further replication studies are needed.