TY - JOUR
T1 - The apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans
AU - Mooser, Vincent
AU - Scheer, Douglas
AU - Marcovina, Santica M.
AU - Wang, Jinping
AU - Guerra, Rudy
AU - Cohen, Jonathan
AU - Hobbs, Helen H.
N1 - Funding Information:
We wish to thank Tommy Hyatt and Melissa Christiansen for excellent technical assistance, and we wish to thank Barbara Gilbert for collecting the blood samples from the families. We would also like to thank Laura Fuller for preparation of the manuscript. We thank Ann White for helpful discussion. H.H.H. is supported by NIH grants HL-47619 and HL-20948 and by the Perot Family Fund, and S.M.M. is supported by NIH grant HL-30086. V.M. was supported by a scholarship from the Swiss Academy for Medical Sciences and, presently, by a SCORE grant from the Swiss National Foundation for Scientific Research. D.S. is supported by the American Diabetes Association.
PY - 1997/8
Y1 - 1997/8
N2 - The distributions of plasma lipoprotein(a), or Lp(a), levels differ significantly among ethnic groups. Individuals of African descent have a two- to threefold higher mean plasma level of Lp(a) than either Caucasians or Orientals. In Caucasians, variation in the plasma Lp(a) levels has been shown to be largely determined by sequence differences at the apo(a) locus, but little is known about either the genetic architecture of plasma Lp(a) levels in Africans or why they have higher levels of plasma Lp(a). In this paper we analyze the plasma Lp(a) levels of 257 sibling pairs from 49 independent African American families. The plasma Lp(a) levels were much more similar in the sibling pairs who inherited both apo(a) alleles identical by descent (IBD) (r = .85) than in those that shared one (r = .48) or no (r = .22) parental apo(a) alleles in common. On the basis of these findings, it was estimated that 78% of the variation in plasma Lp(a) levels in African Americans is attributable to polymorphism at either the apo(a) locus or sequences closely linked to it. Thus, the apo(a) locus is the major determinant of variation in plasma Lp(a) levels in African Americans, as well as in Caucasians. No molecular evidence was found for a common 'high- expressing' apo(a) allele in the African Americans. We propose that the higher plasma levels of Lp(a) in Africans are likely due to a yet-to-be- identified transacting factor(s) that causes an increase in the rate of secretion of apo(a) or a decrease in its catabolism.
AB - The distributions of plasma lipoprotein(a), or Lp(a), levels differ significantly among ethnic groups. Individuals of African descent have a two- to threefold higher mean plasma level of Lp(a) than either Caucasians or Orientals. In Caucasians, variation in the plasma Lp(a) levels has been shown to be largely determined by sequence differences at the apo(a) locus, but little is known about either the genetic architecture of plasma Lp(a) levels in Africans or why they have higher levels of plasma Lp(a). In this paper we analyze the plasma Lp(a) levels of 257 sibling pairs from 49 independent African American families. The plasma Lp(a) levels were much more similar in the sibling pairs who inherited both apo(a) alleles identical by descent (IBD) (r = .85) than in those that shared one (r = .48) or no (r = .22) parental apo(a) alleles in common. On the basis of these findings, it was estimated that 78% of the variation in plasma Lp(a) levels in African Americans is attributable to polymorphism at either the apo(a) locus or sequences closely linked to it. Thus, the apo(a) locus is the major determinant of variation in plasma Lp(a) levels in African Americans, as well as in Caucasians. No molecular evidence was found for a common 'high- expressing' apo(a) allele in the African Americans. We propose that the higher plasma levels of Lp(a) in Africans are likely due to a yet-to-be- identified transacting factor(s) that causes an increase in the rate of secretion of apo(a) or a decrease in its catabolism.
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U2 - 10.1086/514851
DO - 10.1086/514851
M3 - Article
C2 - 9311746
AN - SCOPUS:0030799057
SN - 0002-9297
VL - 61
SP - 402
EP - 417
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -