title: Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians.
abstract: OBJECTIVE
  The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians.
  
  
  METHODS
  We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs.
  
  
  RESULTS
  The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians.
  
  
  CONCLUSIONS
  Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Mahmoud
authors: M
authors: Khalifa
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Asma
authors: A
authors: Noureen
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Kathrin
authors: K
authors: Ertelthalner
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Ahmad Reza
authors: AR
authors: Bandegi
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors: Rhena
authors: R
authors: Delport
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Wance J J
authors: WJ
authors: Firdaus
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Department of Clinical Biochemistry, Christian Medical College Vellore, Tamil Nadu, India.
authors: Finney S
authors: FS
authors: Geethanjali
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors: Kalpana
authors: K
authors: Luthra
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Department of Obstetrics and Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Orawan
authors: O
authors: Makemaharn
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors: Richard W C
authors: RW
authors: Pang
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Abdel-Halim
authors: AH
authors: Salem
authors: Graduate School of Pharmaceutical Medicine, International University of Health and Welfare, Fukuoka, Japan.
authors: Jun
authors: J
authors: Sasaki
authors: Max-Planck-Institute for Ornithology, Andechs, Germany.
authors: Wulf
authors: W
authors: Schiefenhoevel
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Arno
authors: A
authors: Lingenhel
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Florian
authors: F
authors: Kronenberg
authors: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Gerd
authors: G
authors: Utermann
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon; Department for Tropical Medicine, Eberhard-Karls-University Tuebingen, Tuebingen, Germany. Electronic address: konrad.schmidt@i-med.ac.at.
authors: Konrad
authors: K
authors: Schmidt
mesh_terms: D000349:Africa; D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics*; D001208:Asia; D044466:Asian People; D002681:China; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics; D056915:DNA Copy Number Variations; D016521:Electrophoresis, Gel, Pulsed-Field; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D001054:Apolipoproteins A; D005819:Genetic Markers; D020033:Protein Isoforms
keywords: Copy number variation; Coronary artery disease; Genetic variation; Lipoprotein(a); Population genetics