Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.
Plasma lipoprotein [a] (Lp[a]) concentrations are inversely associated with, and largely determined by, apolipoprotein [a] (apo[a]) gene size, a highly polymorphic trait. We studied if, within an individual, the smaller apo[a] isoform always dominated, whether there was interaction between the two alleles, and whether these features differed between Caucasians and African Americans. We determined apo[a] gene sizes, apo[a] protein sizes and relative amounts, and plasma Lp[a] levels in 430 individuals (263 Caucasians and 167 African Americans). Of the 397 heterozygotes with at least one detectable apo[a] isoform (238 Caucasians and 159 African Americans), the larger allele dominated in 28% of Caucasians and 23% of African Americans, while the smaller allele dominated in 56% of Caucasians and 45% of African Americans. In Caucasians, dominance of the smaller allele increased with Lp[a] levels, from 44% at Lp[a] < or = 30 nM to 81% at Lp[a] >100 nM (P < 0.0001). Dominance by the smaller allele increased with increasing size of the larger allele in both groups but with the smaller allele only in African Americans. There was no interaction between apo[a] alleles within genotypes; one apo[a] isoform level was not associated with the other isoform level, and isoform levels were not affected by the difference in size. More of the dominance pattern was explained by Lp[a] level and apo[a] genotype in African Americans than in Caucasians (29% vs. 13%). Thus, genotype influences isoform-specific Lp[a] levels and dominance patterns differently in African Americans and in Caucasians.
Rubin
Jill
J
Department of Medicine, Columbia University, New York, NY 10032, USA.
Paultre
Furcy
F
Tuck
Catherine H
CH
Holleran
Steve
S
Reed
Roberta G
RG
Pearson
Thomas A
TA
Thomas
Christopher M
CM
Ramakrishnan
Rajasekhar
R
Berglund
Lars
L
D000368:Aged; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics*; D001741:Black or African American
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D020033:Protein Isoforms