Submitted on August 10, 2005
Revised on January 30, 2006
Accepted on February 21, 2006
The APO(a) size and PNR polymorphisms explain differences in allele-specific APO(a) levels between African Americans and Caucasians for small APO(a) but not large APO(a) sizes
Jill Rubin, Han Jo Kim, Thomas A. Pearson, Steve Holleran, Rajasekhar Ramakrishnan, and Lars Berglund
Medicine Dept., University of California Davis, Sacramento, CA 95817
Corresponding Author: lars.berglund{at}ucdmc.ucdavis.edu
Objective: Apo(a) gene size is a major predictor of Lp(a) level, a cardiovascular risk factor with large differences between Caucasians and African Americans. To determine genetic predictors of allele-specific apo(a) levels beyond gene size, we evaluated the upstream C/T and PNR polymorphisms. Methods and Results: We determined apo(a) sizes, allele-specific apo(a) levels (i.e. levels associated with alleles defined by size) and the C/T and PNR polymorphisms in 354 men and women (215 Caucasians and 139 African Americans). For Caucasians, the effect of apo(a) size on allele-specific levels was substantially greater in subjects with gene size below 24 K4; for African Americans, the size effect was smaller than in Caucasians below 24 K4 but did not decrease at higher repeats. In both groups the level decreased with increasing size of the other allele. Controlling for apo(a) sizes, PNR influenced allele-specific apo(a) levels in Caucasians, with a stepwise decrease with increasing PNR number >8. The C/T polymorphism had no independent effect on apo(a) levels in either group. In a multiple regression model, apo(a) allele size, the size and expression of the other apo(a) allele (and PNR >8 for Caucasians) significantly predicted allele-specific apo(a) levels. For a common PNR 8 allele, predicted values were similar in the two ethnicities for small-size apo(a) but different otherwise. Conclusion: Allele-specific apo(a) levels were influenced by the other allele size and expression. Observed differences between Caucasians and African Americans in allele-specific apo(a) levels were explained for small apo(a) sizes by the other allele size and the PNR polymorphism; the decrease in levels with size was much greater for Caucasians so the ethnicity differences remain unexplained for larger sizes.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
