Introduction: Ischemic stroke (IS) is an extremely complex disease caused by the combined action of multiple environmental and genetic factors. CYP1B1 is a member of the cytochrome P450 protein family, and it is an important human drug-metabolizing enzymes. We aimed to explore the association between CYP1B1 genetic variants and IS risk in Chinese Han population. Methods: We recruited 1,150 participants to conduct a “case-control” study. The assessment of association between candidate CYP1B1 genetic variants (rs2855658, rs10916, rs162560, rs2567206) and IS risk was performed by SNPStats online software. In addition, false-positive report probability analysis was used to detect whether the positive findings were just chance or noteworthy observations. Finally, the interaction of candidate SNPs in IS risk was evaluated by multifactor dimensionality reduction. Results: The results showed that CYP1B1-rs2855658 was a risk factor for IS among ≥60-year-old (dominant: p = 0.034; overdominant: p = 0.026), smoking (heterozygote: p = 0.009; dominant: p = 0.004; overdominant: p = 0.012; log-additive: p = 0.003), and drinking participants (homozygous: p = 0.036; dominant: p = 0.019; recessive: p = 0.012; log-additive: p = 0.006). CYP1B1-rs10916 also was a risk factor for IS patients among ≥60-year-old (heterozygote: p = 0.047; overdominant: p = 0.048), smoking (dominant: p = 0.050; overdominant: p = 0.049), and drinking participants (dominant: p = 0.019; overdominant: p = 0.038; log-additive: p = 0.013). Conclusion:CYP1B1-rs10916 and CYP1B1-rs2855658 can increase the IS risk in Chinese Han population who are ≥60 years old, smoking, or drinking alcohol.

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