title: The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans.
abstract: 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 trans-acting factor(s) that causes an increase in the rate of secretion of apo(a) or a decrease in its catabolism.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: V
authors.initials: V
authors.lastname: Mooser
authors.forename: D
authors.initials: D
authors.lastname: Scheer
authors.forename: S M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Guerra
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: H H
authors.initials: HH
authors.lastname: Hobbs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016018:Least-Squares Analysis; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D001054:Apolipoproteins A; D017270:Lipoprotein(a)