title: A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease.
abstract: OBJECTIVE
  The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD).
  
  
  RESULTS
  We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12,077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD: LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003).
  
  
  CONCLUSIONS
  The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.
authors.affiliation: Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. may.luke@celera.com
authors.forename: May M
authors.initials: MM
authors.lastname: Luke
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Dongming M
authors.initials: DM
authors.lastname: Liu
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: June
authors.initials: J
authors.lastname: Cassano
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Diane U
authors.initials: DU
authors.lastname: Leong
authors.forename: Andre R
authors.initials: AR
authors.lastname: Arellano
authors.forename: Carmen H
authors.initials: CH
authors.lastname: Tong
authors.forename: Irina
authors.initials: I
authors.lastname: Movsesyan
authors.forename: Josephina
authors.initials: J
authors.lastname: Naya-Vigne
authors.forename: Curtis
authors.initials: C
authors.lastname: Noordhof
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Feric
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Marlys L
authors.initials: ML
authors.lastname: Koschinsky
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
mesh_terms: D000368:Aged; D053241:Apoprotein(a) / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D053241:Apoprotein(a)