A recent case- control study of Chinese women evaluated the association between the single-nucleotide polymorphisms rs10958409 GA/AA (located near SOX17, a transcription factor that modulates cardiovascular development and endothelial cell biology) and rs1333040 CT/TT (located near CDKN2A, CDKN2B, and ANRIL, which regulate p53 activity) and risk of ischemic and hemorrhagic stroke in OC users and nonus- Women with the rs10958409 GA/AA or rs1333040 CT/TT genotypes (associated with susceptibility of intracra- nial aneurysm) had an increased overall risk of stroke, which increased to an OR of 6.06 (95% CI, 1.69 21.81) and 14.48 (95% CI, 1.56 134.43), respectively, in OC users <50 years of age. The rs1333040 single-nucleotide polymorphism was a significant risk with OC use only for hemorrhagic stroke, This study is important because it demonstrates not only the gene-drug interaction but also some potential mecha- nisms for how OCs might lead to hemorrhage in specific at- Additional Risk Factors for Stroke in Women Using OCs Besides the well-established risk associated with older age, cigarette smoking, hypertension, and migraine head- the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study from the Netherlands showed that women who were obese (OR, 4.6; 95% CI, 2.4 8.9) and had a history of hypercholesterolemia (OR, 10.8; 95% CI, 2.3 49.9) were also at an increased risk from OC use compared with women with these risk factors who did not use OCs.224 The RATIO investigators have performed multiple anal- yses to identify prothrombotic mutations in women with stroke who were and were not OC users (Table 8). They found that women using OCs who were heterozygous for factor V Leiden (OR, 11.2; 95% CI, 4.2 29.0) and methyl tetrahydrofolate reductase or MTHFR 677TT mutation (OR, 5.4; 95% CI, 2.4 12.0) were at increased risk of IS. 