title: Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans.
abstract: BACKGROUND
  The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown.
  
  
  OBJECTIVE
  To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a).
  
  
  METHODS
  Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of >2% in European Americans or African Americans, and four new variants.
  
  
  RESULTS
  Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p<0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of <20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%.
  
  
  CONCLUSIONS
  Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: J-P
authors.initials: JP
authors.lastname: Chretien
authors.forename: J
authors.initials: J
authors.lastname: Coresh
authors.forename: Y
authors.initials: Y
authors.lastname: Berthier-Schaad
authors.forename: W H L
authors.initials: WH
authors.lastname: Kao
authors.forename: N E
authors.initials: NE
authors.lastname: Fink
authors.forename: M J
authors.initials: MJ
authors.lastname: Klag
authors.forename: S M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: F
authors.initials: F
authors.lastname: Giaculli
authors.forename: M W
authors.initials: MW
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005787:Gene Frequency; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics / Q000628:therapy; D015810:Linkage Disequilibrium; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D017270:Lipoprotein(a)