Abstract
Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allelespecific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans. For Caucasians, apo[a] size affected allele-specific levels substantially greater in subjects with apo[a] < 24 K4; for African Americans, the size effect was smaller than in Caucasians, <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 decreased allele-specific apo[a] levels in Caucasians with increasing PNR > 8. In a multiple regression model, apo[a] allele size and 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]. 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 PNR; the ethnicity differences remain unexplained for larger sizes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 982-989 |
| Number of pages | 8 |
| Journal | Journal of Lipid Research |
| Volume | 47 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2006 |
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Keywords
- African Americans
- Apolipoprotein [a]
- Genotyping
- Lipoprotein [a]
- Pentanucleotide repeat
- Polymorphism
ASJC Scopus subject areas
- Endocrinology
Cite this
Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]. / Rubin, Jill; Han, Jo Kim; Pearson, Thomas A.; Holleran, Steve; Ramakrishnan, Rajasekhar; Berglund, Lars.
In: Journal of Lipid Research, Vol. 47, No. 5, 05.2006, p. 982-989.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]
AU - Rubin, Jill
AU - Han, Jo Kim
AU - Pearson, Thomas A.
AU - Holleran, Steve
AU - Ramakrishnan, Rajasekhar
AU - Berglund, Lars
PY - 2006/5
Y1 - 2006/5
N2 - Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allelespecific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans. For Caucasians, apo[a] size affected allele-specific levels substantially greater in subjects with apo[a] < 24 K4; for African Americans, the size effect was smaller than in Caucasians, <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 decreased allele-specific apo[a] levels in Caucasians with increasing PNR > 8. In a multiple regression model, apo[a] allele size and 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]. 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 PNR; the ethnicity differences remain unexplained for larger sizes.
AB - Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allelespecific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans. For Caucasians, apo[a] size affected allele-specific levels substantially greater in subjects with apo[a] < 24 K4; for African Americans, the size effect was smaller than in Caucasians, <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 decreased allele-specific apo[a] levels in Caucasians with increasing PNR > 8. In a multiple regression model, apo[a] allele size and 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]. 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 PNR; the ethnicity differences remain unexplained for larger sizes.
KW - African Americans
KW - Apolipoprotein [a]
KW - Genotyping
KW - Lipoprotein [a]
KW - Pentanucleotide repeat
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=33646800494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646800494&partnerID=8YFLogxK
U2 - 10.1194/jlr.M500359-JLR200
DO - 10.1194/jlr.M500359-JLR200
M3 - Article
C2 - 16495513
AN - SCOPUS:33646800494
VL - 47
SP - 982
EP - 989
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 5
ER -