Hypervariable polymorphism of APO(a) in blacks and whites as reflected by phenotyping
M I Kamboh1, C M Svitko, E R Williams
1Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Chemistry and Physics of Lipids
|January 1, 1994
Summary
Genetic variations in apolipoprotein(a) [APO(a)] alleles show significant differences between Black and White populations. These APO(a) size variations may explain differences in LP(a) levels between racial groups.
Area of Science:
- Genetics
- Biochemistry
- Population Health
Background:
- Lipoprotein(a) [LP(a)] levels are a significant risk factor for cardiovascular disease.
- Genetic factors, particularly polymorphisms in the apolipoprotein(a) [APO(a)] gene, play a crucial role in determining LP(a) levels.
- Observed differences in mean LP(a) levels exist between different racial groups, notably between Black and White populations.
Purpose of the Study:
- To investigate and compare the genetic polymorphism of the apolipoprotein(a) [APO(a)] structural locus in American Black and White populations.
- To determine if variations in APO(a) allele frequencies and sizes contribute to the disparities in LP(a) levels between these racial groups.
Main Methods:
- Employed high-resolution SDS-agarose electrophoresis followed by immunoblotting to analyze APO(a) isoforms.
- Screened 203 American Blacks and compared findings with a previously analyzed American White sample using identical methods.
- Documented discrete APO(a) allelic isoforms and calculated gene frequencies and phenotype distributions.
Main Results:
- Identified a total of 27 discrete APO(a) allelic isoforms across both populations, with 24 common to both.
- Observed similar high levels of gene diversity at the APO(a) locus in both Black (93%) and White (94%) populations.
- Found significant differences in APO(a) allele frequencies: large-size alleles (lower LP(a)) were less frequent in Blacks, while medium-size alleles (intermediate LP(a)) were more frequent in Blacks compared to Whites. Small-size alleles (higher LP(a)) frequencies were comparable.
Conclusions:
- The genetic diversity at the APO(a) locus is similar between Black and White populations.
- Significant differences in the frequencies of specific APO(a) allele sizes exist between Blacks and Whites.
- Size variation in APO(a) alleles is a likely explanation for the observed differences in mean LP(a) levels between Black and White individuals, contributing to differential cardiovascular risk.
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