Differential apolipoprotein(a) isoform expression in heterozygosity is an independent contributor to lipoprotein(a) levels variability.
METHODS
Lipoprotein(a) [Lp(a)] levels represent an independent risk factor for cardio- and cerebrovascular diseases. Since lipoprotein(a) levels show a wide variability even in subjects with similar apolipoprotein(a) isoforms, we investigated the contribution of apolipoprotein(a) heterozygosity to lipoprotein(a) variance. Lipoprotein(a) levels, apolipoprotein(a) isoforms identification and expression, and the correlation with other lipo-apolipoprotein parameters have been investigated in 628 subjects >18 years of age.


RESULTS
In our study, 246 subjects were found heterozygous for apolipoprotein(a) isoforms. Lipoprotein(a) levels were higher in females. About 40% of the subjects expressed the larger isoform more intensely than the dominant isoform. Lipoprotein(a) was correlated with apolipoprotein(a) dominant isoform size, HDL-cholesterol and smaller apolipoprotein(a) isoform expression rate. Lipoprotein(a) was independently correlated with the smaller apolipoprotein(a) isoform, with its expression rate and with LDL-cholesterol. The inclusion of the smaller apolipoprotein(a) expression rate in a multiple regression model explained at least an additional 4% of the lipoprotein(a) variance after correction for apolipoprotein(a) size.


CONCLUSIONS
The smaller isoforms are not always effectively dominant in heterozygosis since 40% of the subjects expressed more the larger isoform. The individual variability of apolipoprotein(a) isoform expression in heterozygosis could explain part of the lipoprotein(a) levels variability.
Noto
Davide
D
Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy.
Pace
Antonio
A
Cefalù
Angelo B
AB
Barbagallo
Carlo M
CM
Rizzo
Manfredi
M
Marino
Giuseppina
G
Emmanuele
Giovanni
G
Travali
Salvatore
S
Notarbartolo
Alberto
A
Averna
Maurizio
M
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000235:genetics*; D053241:Apoprotein(a); D005260:Female; D006579:Heterozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms
D001053:Apolipoproteins; D017270:Lipoprotein(a); D020033:Protein Isoforms; D053241:Apoprotein(a)