03078nas a2200325   4500008004100000245012300041210006900164300001300233490000700246520214700253100002002400700001302420700001802433700002102451700001102472700001802483700001602501700001902517700001802536700001902554700001702573700001802590700001502608700001802623700001902641700002202660700001702682700001702699856003602716       2019                        eng d00a{The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)0 aimpact of APOE genotype on survival Results of 38537 participant  ae02196680 v143 aApolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-Îµ4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-Îµ2 allele on diseases in the elderly and survival remains elusive.\ We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-Îµ2, with survival in the population.\ During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-Îµ3 carriers, APOE-Îµ2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-Îµ4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-Îµ2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-Îµ4 (HR 1.52,1.37-1.70). After censoring for dementia, effect estimates remained similar for APOE-Îµ2 (HR 0.95,0.90-1.01), but attenuated for APOE-Îµ4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for Îµ2 versus Îµ33: -17.1(-18.1-16.0), and Îµ4 versus Îµ33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities.\ Compared with APOE-Îµ3, APOE-Îµ2 is associated with prolonged survival, whereas mortality risk is increased for APOE-Îµ4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-Îµ2 in health and disease.1 aWolters, F., J.1 aYang, Q.1 aBiggs, M., L.1 aJakobsdottir, J.1 aLi, S.1 aEvans, D., S.1 aBis, J., C.1 aHarris, T., B.1 aVasan, R., S.1 aZilhao, N., R.1 aGhanbari, M.1 aIkram, M., A.1 aLauner, L.1 aPsaty, B., M.1 aTranah, G., J.1 aKulminski, A., M.1 aGudnason, V.1 aSeshadri, S.  uhttps://chs-nhlbi.org/node/8531