APOL1Risk Variants Associate with the Prevalence of Stroke in African American Current and Past Smokers

Abstract

ABSTRACTIntroductionAmong 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 showedAPOL1G1/G2 risk variants associate with stroke. However, the role ofAPOL1variants in tobacco-related stroke is unknown.MethodsIn a cross-sectional study, we examined whetherAPOL1risk 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 determinedAPOL1variants, smoking status, and history of stroke. Using unstratified and stratified multivariable logistic regression models we examined the association between smoking history (eversmokers vs.neversmokers) and odds of stroke overall, and among carriers of risk variants and non-carriers, separately.ResultsAmong participants, 41% wereever(currentandpast) smokers, 54% were carriers of theAPOL1risk 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 byAPOL1genotype status in the unstratified model (Pinteraction term=0.016). Among carriers of risk variants,eversmokers had odds ratio (OR) =2.88 for stroke compared toneversmokers (P=0. 0.038). The OR for stroke comparingevervs.neversmokers 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.ConclusionIn conclusion, current and past smokers who carryAPOL1G1 and/or G2 risk variants may be more susceptible to stroke, in particular ischemic stroke, among African Americans.