1887

Abstract

Abstract

Dyslipidemia is a complex phenotype that depends on gene-environment interactions to be manifested. Deleterious mutations in proteins of the lipid transport pathway are expected to contribute to dyslipidemias. Apolipoprotein E (ApoE), a protein component of blood lipid particles, plays an important role in lipid transport and delivery. Single polymorphisms in residues 112 and 158 define the common E2, E3 and E4 alleles. In a study of Qataris, we observed that 17.4 percent of the African-derived genetic subgroup were heterozygotes for the rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with dyslipidemia. Based on this, we hypothesized that the R145C polymorphism may be common in African-derived populations. The prevalence of the R145C variant worldwide was assessed in the 1000 Genomes Project (1000G) and then in 1012 Caucasians and 1226 African-Americans in New York City. Lipid profiles of the Qatari and New York R145C+ heterozygotes were compared to controls. R145C+ Qatari heterozygotes had higher triglyceride levels compared to Qatari controls (p<0.007). The 1000Gs data demonstrated that the R145C polymorphism is rare in non-African derived populations, but present in 4.9-12.3 percent of sub-Saharan African-derived populations. The R145C polymorphism was rare in New York City Caucasians (1/1012, 0.1%), but strikingly, 53 (4.3 percent) of 1,226 New York City African-Americans were R145C+ heterozygotes, with an average of 52 percent higher fasting triglyceride levels compared to African-American R145C- controls (p<0.002).

Based on these observations, there are likely to be millions of people worldwide derived from sub-Saharan Africans that are ApoE R145C+. While larger epidemiologic studies will be necessary to determine the long-term consequences of this polymorphism and the environmental and genetic factors contributing to severe manifestation of dyslipidemia in a subset of carriers, the available evidence suggests it is a common cause of triglyceride dyslipidemia.

Maen D. Abou Ziki, Yael Strulovici-Barel, Neil R. Hackett, Juan L. Rodriguez-Flores, Jason G. Mezey, Jacqueline Salit, Sharon Radisch, Charleen Hollmann, Lotfi Chouchane, Joel Malek, Mahmoud A. Zirie, Amin Jayyuosi, Antonio M. Gotto, Jr, and Ronald G. Crystal

Loading

Article metrics loading...

/content/papers/10.5339/qproc.2012.mutagens.3.77
2012-03-01
2019-10-14
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.77
Loading
  • Received: 15 May 2012
  • Accepted: 15 May 2012
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error