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.

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique

“…Part of the β-globin locus was amplified as an internal control PCR fragment (540 bp). According to a published PCR-SSP protocol [29,30], 20 ng DNA were subjected to 10 μl PCR reactions including 0.5 μM each allele-specific primers, 0.1 μM each internal control primer, standard PCR buffer (Qiagen), 200 μM each dNTP and 0.5 units Taq DNA polymerase (Qiagen). The cycling conditions were: 2 min initial denaturation at 94°C, followed by 10 cycles with 20 s denaturation at 94°C and 1 min annealing/extension at 65°C, followed by 20 cycles with 20 s duration at 94°C, 1 min annealing at 61°C and 30 s extension at 72°C.…”

Immune activation by a multigene family of lectins with variable tandem repeats in oriental river prawn ( Macrobrachium nipponense )

“…In prokaryotes, the collagen-like protein (BclA) is the first identified Bacillus anthracis protein that contain an internal collagen-like region of GXX repeats, which is associated with phenotypic variation [26]. In vertebrates, VNTR polymorphism in the P-selectin glycoprotein ligand 1 gene has been associated with ischaemic cerebrovascular disease [27]. In humans, host defence proteins do not have an excess of tandem repeat variation [11].…”

P-selectin glycoprotein ligand-1 variable number of tandem repeats polymorphism in young myocardial infarction patients

“…Adhesion of circulating leukocytes to injured endothelium is the first step [5][6][7]. The selectin family plays a role in initiating this cascade [5][6][7][8]. P-selectin (PSEL), a member of the selectin family, initiates leukocyte rolling, and plays a role in leukocyte-endothelium, platelet-endothelium and leukocyte-platelet interaction [6][7][8][9].…”

“…The selectin family plays a role in initiating this cascade [5][6][7][8]. P-selectin (PSEL), a member of the selectin family, initiates leukocyte rolling, and plays a role in leukocyte-endothelium, platelet-endothelium and leukocyte-platelet interaction [6][7][8][9]. In order to perform its actions, PSEL needs a counter-ligand [6][7][8][9].…”

“…P-selectin (PSEL), a member of the selectin family, initiates leukocyte rolling, and plays a role in leukocyte-endothelium, platelet-endothelium and leukocyte-platelet interaction [6][7][8][9]. In order to perform its actions, PSEL needs a counter-ligand [6][7][8][9]. The major ligand of PSEL is P-selectin glycoprotein ligand-1 (PSGL-1), expressed in myeloid cells and localized in the coding region of the gene; it controls the initial interaction between leukocytes, platelets and endothelium [7,[9][10][11].…”