Objective The renin-angiotensin-aldosterone system is important for cerebrovascular research because it influences blood pressure, vasoconstriction, thrombosis, and vessel wall damage. We hypothesized that genetic variations in CYP11B2 gene might contribute to the susceptibility for stroke. Methods and results Here, we present genetic association analyses on CYP11B2 gene variants in two independent ischemic stroke (IS) cohorts. Four single nucleotide polymorphisms (SNPs) from CYP11B2 gene were genotyped in 558 Chinese patients and 557 matched controls. Another replication was conducted in an independent sample of 525 IS cases and 694 controls. In addition, meta-analyses was performed to assess the association between the rs1799998 (-344C/T) CYP11B2 polymorphism and IS. Only one SNP rs1799998 (-344C/T) showed association with overall IS in the first study (P-dominant=0.003, P-additive=0.003, respectively), but this was not replicated in our second cohort. No associations were found for the rest of SNPs in both the studies. Meta-analyses (including our study) revealed that -344C/T of CYP11B2 was associated with IS both in a dominant effect (odds ratio=1.51, 95% Cl: 1.06-2.16, P=0.023) and a recessive effect (odds ratio=1.57, 95% Cl: 1.14-2.16). Above all, our results suggest that genetic variation rs1799998 (-344C/T) of CYP11B2 gene may contribute to the risk of IS with moderate effect in Han Chinese population. Pharmacogenetics and Genomics 21:115-120 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.