Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for ϵ2, ϵ3, and ϵ4, respectively, in African Americans and 0.08, 0.78, and 0.14 for ϵ2, ϵ3, and ϵ4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 ϵ2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 ϵ3 carriers and 43 of 92 ϵ4 carriers (48% and 47%, respectively), suggesting a protective effect of the ϵ2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in ϵ2 carriers than in ϵ3 and ϵ4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in ϵ2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 the lipid We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for ϵ2, ϵ3, and ϵ4, respectively, in African Americans and 0.08, 0.78, and 0.14 for ϵ2, ϵ3, and ϵ4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 ϵ2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 ϵ3 carriers and 43 of 92 ϵ4 carriers (48% and 47%, respectively), suggesting a protective effect of the ϵ2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in ϵ2 carriers than in ϵ3 and ϵ4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in ϵ2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 the lipid E (apoE) a in the of cholesterol and the of of and a and the of and to the LDL than a lipid ϵ3, and allele one and in and and of the apolipoprotein E and to of the apolipoprotein E for of the of LDL cholesterol levels, a with in the E and and at the in to of coronary E and a of apolipoprotein E to and coronary artery with ϵ3 carriers of the ϵ2 allele lower cholesterol and levels, whereas the ϵ4 allele with of and LDL cholesterol of by a the relationship between and coronary artery disease (CAD) of apolipoprotein E and of in in with coronary with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the a association of with to CAD with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E of the of lipid in and allele as as the ϵ4 allele with a The apolipoprotein allele and the effect of in of a of the E in a of allele with and to lipid E in a compared to in the of apolipoprotein in of to and to of the whereas difference in apolipoprotein E allele frequencies between the and of the apolipoprotein and E and relationship to lipid in of in the of and of apolipoprotein E in association with coronary disease and lipid The of apolipoprotein E the of and in the and E in and to and The profile of a of E and and to frequencies of the ϵ2 and ϵ4 the ϵ4 allele African Americans of with lipid in a of apolipoprotein E with in and The in of of apolipoprotein E in E and association with in the In Caucasians, the ϵ4 allele with LDL cholesterol levels, and whereas the ϵ2 allele to be a lack of the of CAD African In the of lipid in of the in Caucasians and African Americans, and lipid in to the presence of disease were a for diagnostic coronary at in at the in The and African in for but not of with a with coronary artery disease in African and and as African were for the of in African Americans, 326 for lipid and were The was by the at the of and and the of and was were the and and were at of and and were for the of of for of cholesterol were of with for of LDL cholesterol were in with of with the of and of the of cholesterol in of the of and were for LDL was the was a at of isoforms were at the by the and as of the of at the apolipoprotein E in for the The were with the and a as by and of apolipoprotein E by and with to and the and of for of the coronary The presence of CAD was defined as at least stenosis in of coronary artery was of the presence of stenosis a of coronary artery of was with as and and were to were compared between and were compared for CAD and were for and for and and were with the for was to the and significantly to the the presence of a P < was to of the in In with CAD were and significantly of and LDL and compared with In African Americans, with CAD significantly of and compared with and were CAD significantly (P < compared with CAD of Caucasians and African Americans undergoing coronary CAD CAD cholesterol LDL cholesterol cholesterol apolipoprotein coronary artery (P were for and for and and were with the for for and were was of the presence of stenosis a of coronary artery in a African Americans a significantly of the ϵ4 allele vs. P < and a significantly lower of the ϵ3 allele vs. P < compared with Caucasians In were ϵ2 carriers and ϵ3 carriers and ϵ4 carriers and with the were of the effect of ϵ2 and ϵ4 lipid of African Americans and Caucasians in In African Americans, of LDL cholesterol were significantly lower ϵ2 carriers compared with carriers in Caucasians, were no such in LDL cholesterol Caucasians of compared with African Americans were significantly ϵ2 carriers compared with ϵ3 and ϵ4 Among African Americans, but not Caucasians, were significantly lower ϵ2 carriers compared with ϵ3 and ϵ4 carriers and were in ϵ4 carriers compared with ϵ2 and ϵ3 carriers the not and allele frequencies in to CAD CAD in a Among African Americans, CAD was present in 9 of 34 ϵ2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 ϵ3 carriers and 43 of 92 ϵ4 carriers (48% and 47%, In Caucasians, the CAD were of 39 ϵ2 carriers, of ϵ3 carriers, and 39 of carriers ϵ4 carriers and respectively), not significantly one The in African Americans was significantly (P lower ϵ2 carriers compared with ϵ3 and ϵ4 carriers and In was no such difference in in Caucasians disease < ϵ2 carriers carriers in African and P < ϵ2 carriers carriers in African in a We to the and significantly to the presence of disease In ϵ2 was significantly with CAD P in African In a adjusting for LDL the association between apoE2 and CAD was no longer (P The P for and presence of the protective effect of apoE2 in African Americans could be explained by a favorable effect of the ϵ2 allele lipid whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 the lipid in African Americans to in ϵ2 and LDL cholesterol in ϵ2 LDL cholesterol ϵ2 LDL cholesterol cholesterol in a the ϵ2 allele was with a lower of disease in African the protective effect of ϵ2 in African Americans was lower LDL cholesterol The ϵ4 in as a for was not with CAD in African Americans the of at the cholesterol and of apolipoprotein E and of in in with coronary with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the to of coronary artery of a as as CAD with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E the the to CAD not The of of LDL and and in apoE2 with lower and LDL cholesterol and with The apolipoprotein E a of allele frequencies and in the relationship between and of and E and and of by a E and African Americans a ϵ4 allele than Caucasians, the association between and lipid CAD the In a effect of and LDL cholesterol and African Americans, but not Caucasians, with lower ϵ2 carriers compared with the of the ϵ2 allele lower LDL cholesterol be by the of cholesterol and E and and of by a E and In with of apolipoprotein E with in and The in in and a of African and in African Americans, and with and Caucasians of compared with African the lower in African Americans a favorable effect of the whereas a protective effect of ϵ2 in Caucasians be by lipid were of CAD in to the ϵ2 allele a protective effect effect lipid In a association of the ϵ2 allele with the presence of CAD in African Americans but not in Caucasians. The ϵ2 allele to a for CAD in in with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E E and to the whereas a lack of such to coronary African Americans of apolipoprotein E with in and The in In a of with lipid in a the ϵ2 allele was with lower LDL cholesterol in Caucasians, and African Americans In the ϵ2 allele was no longer with the presence of the and P for ϵ2 were not in the compared with the the ϵ2 allele Thus, effect lipid in the of CAD and E and and of apolipoprotein E in to in apolipoprotein E (apoE) in not association of the ϵ4 allele with the presence of CAD in African Americans Caucasians. 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of the of LDL cholesterol levels, a with in the E and and at the in to of coronary E and a of apolipoprotein E to and coronary artery with ϵ3 carriers of the ϵ2 allele lower cholesterol and levels, whereas the ϵ4 allele with of and LDL cholesterol of by a the relationship between and coronary artery disease (CAD) of apolipoprotein E and of in in with coronary with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the a association of with to CAD with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E of the of lipid in and allele as as the ϵ4 allele with a The apolipoprotein allele and the effect of in of a of the E in a of allele with and to lipid E in a compared to in the of apolipoprotein in of to and to of the whereas difference in apolipoprotein E allele frequencies between the and of the apolipoprotein and E and relationship to lipid in of in the of and of apolipoprotein E in association with coronary disease and lipid The of apolipoprotein E the of and in the and E in and to and The profile of a of E and and to frequencies of the ϵ2 and ϵ4 the ϵ4 allele African Americans of with lipid in a of apolipoprotein E with in and The in of of apolipoprotein E in E and association with in the In Caucasians, the ϵ4 allele with LDL cholesterol levels, and whereas the ϵ2 allele to be a lack of the of CAD African In the of lipid in of the in Caucasians and African Americans, and lipid in to the presence of disease were a for diagnostic coronary at in at the in The and African in for but not of with a with coronary artery disease in African and and as African were for the of in African Americans, 326 for lipid and were The was by the at the of and and the of and was were the and and were at of and and were for the of of for of cholesterol were of with for of LDL cholesterol were in with of with the of and 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carriers ϵ4 carriers and respectively), not significantly one The in African Americans was significantly (P lower ϵ2 carriers compared with ϵ3 and ϵ4 carriers and In was no such difference in in Caucasians disease < ϵ2 carriers carriers in African and P < ϵ2 carriers carriers in African in a We to the and significantly to the presence of disease In ϵ2 was significantly with CAD P in African In a adjusting for LDL the association between apoE2 and CAD was no longer (P The P for and presence of the protective effect of apoE2 in African Americans could be explained by a favorable effect of the ϵ2 allele lipid whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 the lipid in African Americans to in ϵ2 and LDL cholesterol in ϵ2 LDL cholesterol ϵ2 LDL cholesterol cholesterol in a of the in In with CAD were and significantly of and LDL and compared with In African Americans, with CAD significantly of and compared with and were CAD significantly (P < compared with CAD apolipoprotein coronary artery (P were for and for and and were with the for for and were was of the presence of stenosis a of coronary artery African Americans a significantly of the ϵ4 allele vs. P < and a significantly lower of the ϵ3 allele vs. P < compared with Caucasians In were ϵ2 carriers and ϵ3 carriers and ϵ4 carriers and with the were of the effect of ϵ2 and ϵ4 lipid of African Americans and Caucasians in In African Americans, of LDL cholesterol were significantly lower ϵ2 carriers compared with carriers in Caucasians, were no such in LDL cholesterol Caucasians of compared with African Americans were significantly ϵ2 carriers compared with ϵ3 and ϵ4 Among African Americans, but not Caucasians, were significantly lower ϵ2 carriers compared with ϵ3 and ϵ4 carriers and were in ϵ4 carriers compared with ϵ2 and ϵ3 carriers the not Among African Americans, CAD was present in 9 of 34 ϵ2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 ϵ3 carriers and 43 of 92 ϵ4 carriers (48% and 47%, In Caucasians, the CAD were of 39 ϵ2 carriers, of ϵ3 carriers, and 39 of carriers ϵ4 carriers and respectively), not significantly one The in African Americans was significantly (P lower ϵ2 carriers compared with ϵ3 and ϵ4 carriers and In was no such difference in in Caucasians and We to the and significantly to the presence of disease In ϵ2 was significantly with CAD P in African In a adjusting for LDL the association between apoE2 and CAD was no longer (P The P for and presence of the protective effect of apoE2 in African Americans could be explained by a favorable effect of the ϵ2 allele lipid whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 the lipid the ϵ2 allele was with a lower of disease in African the protective effect of ϵ2 in African Americans was lower LDL cholesterol The ϵ4 in as a for was not with CAD in African Americans the of at the cholesterol and of apolipoprotein E and of in in with coronary with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the to of coronary artery of a as as CAD with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E the the to CAD not The of of LDL and and in apoE2 with lower and LDL cholesterol and with The apolipoprotein E a of allele frequencies and in the relationship between and of and E and and of by a E and African Americans a ϵ4 allele than Caucasians, the association between and lipid CAD the In a effect of and LDL cholesterol and African Americans, but not Caucasians, with lower ϵ2 carriers compared with the of the ϵ2 allele lower LDL cholesterol be by the of cholesterol and E and and of by a E and In with of apolipoprotein E with in and The in in and a of African and in African Americans, and with and Caucasians of compared with African the lower in African Americans a favorable effect of the whereas a protective effect of ϵ2 in Caucasians be by lipid were of CAD in to the ϵ2 allele a protective effect effect lipid In a association of the ϵ2 allele with the presence of CAD in African Americans but not in Caucasians. The ϵ2 allele to a for CAD in in with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E E and to the whereas a lack of such to coronary African Americans of apolipoprotein E with in and The in In a of with lipid in a the ϵ2 allele was with lower LDL cholesterol in Caucasians, and African Americans In the ϵ2 allele was no longer with the presence of the and P for ϵ2 were not in the compared with the the ϵ2 allele Thus, effect lipid in the of CAD and E and and of apolipoprotein E in to in apolipoprotein E (apoE) in not association of the ϵ4 allele with the presence of CAD in African Americans Caucasians. The ϵ4 allele in as a for CAD with the apolipoprotein allele of coronary disease in a of E and to the E and disease in the the allele of coronary of association between coronary disease in and the frequencies of in the for apolipoprotein to such a to of coronary artery of a E with but not with the E and artery the E and artery in a of In the The apolipoprotein allele and the effect of in of a of the the ϵ4 allele of coronary compared with not the allele. not difference in ϵ4 between CAD and in in were for coronary and for the was the with a of be a of compared with the at the allele was to for and E and the of in and of in a the ϵ4 allele was in with and CAD for African Americans vs. and Caucasians vs. the in effect of the ϵ2 allele African Americans and the protective effect of the ϵ2 allele to the for In the ϵ2 allele was with a lower of disease in African the protective effect of ϵ2 in African Americans was lower LDL cholesterol The ϵ4 in as a for was not with CAD in African Americans Caucasians. the of at the cholesterol and of apolipoprotein E and of in in with coronary with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the to of coronary artery of a as as CAD with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E the the to CAD not The of of LDL and and in apoE2 with lower and LDL cholesterol and with The apolipoprotein E a of allele frequencies and in the relationship between and of and E and and of by a E and African Americans a ϵ4 allele than Caucasians, the association between and lipid CAD the In a effect of and LDL cholesterol and African Americans, but not Caucasians, with lower ϵ2 carriers compared with the of the ϵ2 allele lower LDL cholesterol be by the of cholesterol and E and and of by a E and In with of apolipoprotein E with in and The in in and a of African and in African Americans, and with and Caucasians of compared with African the lower in African Americans a favorable effect of the whereas a protective effect of ϵ2 in Caucasians be by lipid were of CAD in to the ϵ2 allele a protective effect effect lipid In a association of the ϵ2 allele with the presence of CAD in African Americans but not in Caucasians. The ϵ2 allele to a for CAD in in with the apolipoprotein allele of coronary disease in a of The apolipoprotein allele and the effect of in of a of the the of not significantly by the apolipoprotein E E and to the whereas a lack of such to coronary African Americans of apolipoprotein E with in and The in In a of with lipid in a the ϵ2 allele was with lower LDL cholesterol in Caucasians, and African Americans In the ϵ2 allele was no longer with the presence of the and P for ϵ2 were not in the compared with the the ϵ2 allele Thus, effect lipid in the of CAD and E and and of apolipoprotein E in to in apolipoprotein E (apoE) in In not association of the ϵ4 allele with the presence of CAD in African Americans Caucasians. The ϵ4 allele in as a for CAD with the apolipoprotein allele of coronary disease in a of E and to the E and disease in the the allele of coronary of association between coronary disease in and the frequencies of in the for apolipoprotein to such a to of coronary artery of a E with but not with the E and artery the E and artery in a of In the The apolipoprotein allele and the effect of in of a of the the ϵ4 allele of coronary compared with not the allele. not difference in ϵ4 between CAD and in in were for coronary and for the was the with a of be a of compared with the at the allele was to for and E and the of in and of in a the ϵ4 allele was in with and CAD for African Americans vs. and Caucasians vs. In the in effect of the ϵ2 allele African Americans and the protective effect of the ϵ2 allele to the for was by and the and was in by the of