title: LPA and PLG sequence variation and kringle IV-2 copy number in two populations.
abstract: OBJECTIVE
  Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic LPA kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations.
  
  
  METHODS
  To identify potential cis-acting factors, we re-sequenced the gene LPA for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen (PLG) and genotyped the kringle IV copy number variant in the same reference samples.
  
  
  RESULTS
  These data are the most comprehensive description of sequence variation in LPA and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of LPA sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within PLG are not in linkage disequilibrium with SNPs in LPA, and we show that kringle IV copy number variation is not in linkage disequilibrium with either LPA or PLG SNPs.
  
  
  CONCLUSIONS
  Together, these data suggest that LPA SNPs could independently contribute to Lp(a) levels in the general population.
authors.affiliation: Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA. crawford@chgr.mc.vanderbilt.edu
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Ze
authors.initials: Z
authors.lastname: Peng
authors.forename: Jan-Fang
authors.initials: JF
authors.lastname: Cheng
authors.forename: Dario
authors.initials: D
authors.lastname: Boffelli
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ahearn
authors.forename: Dan
authors.initials: D
authors.lastname: Nguyen
authors.forename: Tristan
authors.initials: T
authors.lastname: Shaffer
authors.forename: Qian
authors.initials: Q
authors.lastname: Yi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Livingston
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rieder
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D044383:Black People / Q000235:genetics; D018628:Gene Dosage; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D018082:Kringles / Q000235:genetics*; D015810:Linkage Disequilibrium; D017270:Lipoprotein(a) / Q000235:genetics*; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D017270:Lipoprotein(a); D010958:Plasminogen