title: The variable number of tandem repeat polymorphism in the P-selectin glycoprotein ligand-1 gene is not associated with coronary heart disease.
abstract: Genes involved in inflammatory processes are candidates for predisposition to prothrombotic syndromes. The variable number of tandem repeat (VNTR) polymorphism in the P-selectin glycoprotein ligand (PSGL)-1 gene has been associated with ischemic cerebrovascular disease but not with coronary heart disease (CHD). We assessed the effect of the VNTR polymorphism on CHD in two independent case/control studies. In the first study 281 CHD patients and 397 healthy blood donors were genotyped for the VNTR alleles in PSGL-1. The prevalence of homozygous carriers of the PSGL-1 VNTR allele with 15 repeat units was significantly higher in the CHD patients (5.3% vs. 1.5%) than in controls, suggesting an effect of this marker in CHD. To validate the findings genotyping was performed in a second study including 2,578 CHD patients, 731 patients without CHD, and 1084 healthy blood donors. The larger case control study had a power of 99.9% to detect the initially observed difference but failed to confirm the putative role of PSGL-1 VNTR polymorphism in CHD. Frequencies of the PSGL-1 VNTR 15 repeats for homozygous carriers were 2.2% in healthy blood donors, 2.3% in patients without CHD and 2.7%, in CHD cases, respectively. These results demonstrate that the PSGL-1 VNTR polymorphism is not a genetic risk factor for CHD. Adequately powered studies are prerequisites to obtain reliable results about genotype-phenotype relationships of new candidate genes in complex diseases.
authors.affiliation: Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-Hessia, Ruprecht Karl University Heidelberg, Faculty of Clinical Medicine Mannheim, Friedrich-Ebert-Strasse 107, 68167 Mannheim, Germany. p.bugert@blutspende.de
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Marion
authors.initials: M
authors.lastname: Vosberg
authors.forename: Jürgen
authors.initials: J
authors.lastname: Jahn
authors.forename: Matthias
authors.initials: M
authors.lastname: Entelmann
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Siegfried
authors.initials: S
authors.lastname: Goerg
authors.forename: Harald
authors.initials: H
authors.lastname: Klüter
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein