Prevalence of the apolipoprotein E Arg145Cys dyslipidemia at-risk polymorphism in African-derived populations.
Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p <0.007) and the New York African-American R145C subjects had an average of 52% greater fasting triglyceride levels than the New York African-American controls (p <0.002). From these observations, likely millions of people worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia.
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; Department of Genetic Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar.
Maen D
MD
Abou Ziki
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Yael
Y
Strulovici-Barel
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Neil R
NR
Hackett
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Juan L
JL
Rodriguez-Flores
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York.
Jason G
JG
Mezey
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Jacqueline
J
Salit
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Sharon
S
Radisch
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Charleen
C
Hollmann
Department of Genetic Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar.
Lotfi
L
Chouchane
Department of Genetic Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar.
Joel
J
Malek
Department of Medicine, Hamad Medical Corporation, Doha, Qatar.
Mahmoud A
MA
Zirie
Department of Medicine, Hamad Medical Corporation, Doha, Qatar.
Amin
A
Jayyuosi
Department of Medicine, Weill Cornell Medical College, New York, New York.
Antonio M
AM
Gotto
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address: geneticmedicine@med.cornell.edu.
Ronald G
RG
Crystal
D001741:Black or African American; D000483:Alleles; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D050171:Dyslipidemias / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009518:New York / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors
D001057:Apolipoproteins E; D004247:DNA