APOL1 Risk Variants Associate With the Prevalence of Stroke in African American Current and Past Smokers.

BACKGROUND: African American smokers have 2.5 times higher risk for stroke compared with nonsmokers (higher than other races). About 50% of the African American population carry 1 or 2 genetic variants (G1 and G2; rare in other races) of the apolipoprotein L1 gene (APOL1). Studies showed these variants may be associated with stroke. However, the role of the APOL1 risk variants in tobacco-related stroke is unknown. METHODS AND RESULTS: In a cross-sectional study, we examined whether APOL1 risk variants modified the relationship between tobacco smoking and stroke prevalence in 513 African American adults recruited at University of California, San Francisco. Using DNA, plasma, and questionnaires we determined APOL1 variants, smoking status, and stroke prevalence. Using logistic regression models, we examined the association between smoking (ever versus never smokers) and stroke overall, and among carriers of APOL1 risk variants (1 or 2 risk alleles), and noncarriers, separately. Among participants, 41% were ever (current and past) smokers, 54% were carriers of the APOL1 risk variants, and 41 had a history of stroke. The association between smoking and stroke differed by APOL1 genotype (Pinteraction term=0.014). Among carriers, ever versus never smokers had odds ratio (OR) 2.46 (95% CI, 1.08-5.59) for stroke (P=0.034); OR 2.00 (95% CI, 0.81-4.96) among carriers of 1 risk allele, and OR 4.72 (95% CI, 0.62-36.02) for 2 risk alleles. Among noncarriers, smoking was not associated with a stroke. CONCLUSIONS: Current and past smokers who carry APOL1 G1 and/or G2 risk variants may be more susceptible to stroke among the African American population.

APOL1 Risk Variants Associate with the Prevalence of Stroke in African American Current and Past Smokers.

Introduction: Among African Americans, tobacco smokers have 2.5 times higher risk for stroke compared to non-smokers; the tobacco-related stroke risk being higher than in other races/ethnicities. About one half of African Americans carry at least one of two genetic variants (G1 and G2; rare in other races) of apolipoprotein L1 (apoL1), a component of high-density lipoproteins. Several studies showed APOL1 G1/G2 risk variants associate with stroke. However, the role of APOL1 variants in tobacco-related stroke is unknown. Methods: In a cross-sectional study, we examined whether APOL1 risk variants modify the relationship between smoking and stroke in 513 African American adults (median age 58 years, 52% female) recruited through the University of California, San Francisco Lipid Clinic. Using DNA, plasma, and questionnaires we determined APOL1 variants, smoking status, and history of stroke. Using unstratified and stratified multivariable logistic regression models we examined the association between smoking history (ever smokers vs. never smokers) and odds of stroke overall, and among carriers of risk variants and non-carriers, separately. Results: Among participants, 41% were ever (current and past) smokers, 54% were carriers of the APOL1 risk variant, and 41 have had stroke. In all stroke cases, where full medical records were available, stroke types were determined to be an ischemic, and not hemorrhagic, stroke. The association of smoking history and stroke differed by APOL1 genotype status in the unstratified model (Pinteraction term=0.016). Among carriers of risk variants, ever smokers had odds ratio (OR) =2.88 for stroke compared to never smokers (P=0. 0.038). The OR for stroke comparing ever vs. never smokers showed a dose-response trend among carriers of one risk allele of 2.35 and two risk alleles of 4.96. Among non-carriers, smoking history was not associated with a stroke. Conclusion: In conclusion, current and past smokers who carry APOL1 G1 and/or G2 risk variants may be more susceptible to stroke, in particular ischemic stroke, among African Americans.