RESUMO
P-selectin (SELP) and its counter-receptor, P-selectin glycoprotein ligand-1 (PSGL-1), play key role in the transient attachment of leukocytes to endothelial cells predisposing to coronary heart disease (CHD). In the current report, 293 angiographically proven CHD patients and 327 age, gender, and race-matched controls were included. Our aim was to evaluate the contribution to CHD of the following SNPs: C-2123G, G-1969A and T715P in SELP, Met62Ile and the VNTR variants in PSGL-1 gene in a North African population from Tunisia. While there were no significant differences in the distribution of SELP or PSGL-1 alleles or genotypes between patients and controls, a trend for a significant association of the C-2123G genotypes distribution with incident CHD was observed (P=0.06). Assuming an additive model of transmission, the risk was 74% higher among subjects carrying the GG genotypes in comparison to those carrying the CC genotype (OR=1.74 [1.01-2.98], P=0.04) and 80% higher in the recessive model (OR=1.80 [1.08-3.01], P=0.02). Haplotype analysis did not identify any specific SELP or PSGL-1 haplotypes to be associated with CHD. The present study demonstrated no evidence of association between individual SELP or PSGL-1 SNPs or haplotypes with incident CHD. However, this study replicates absence of association of the mostly studied SNP, T715P, previously reported in individuals with African origin.
Assuntos
Doença das Coronárias/genética , Predisposição Genética para Doença , Haplótipos/genética , Glicoproteínas de Membrana/genética , Selectina-P/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , TunísiaRESUMO
Despite extensive exploration of many genes, strong evidence of a molecular genetic association with coronary heart disease (CHD) or myocardial infarction (MI) remains to be obtained. Recently, significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome studies association generating promoting data that will determine the genetic contribution to common human diseases such as coronary heart disease. The aim of the present case-control study including 324 healthy controls and 296 patients with coronary heart disease from Tunisia, was to assess relation between three polymorphisms previously reported to be strongly associated with coronary heart disease in the Welcome Trust Case Control Consortium (WTCCC) and the German myocardial infarction family studies: locus 9p21.3 (rs 1333049), locus 6q25.1 (rs6922269) and 2q36.3 (rs2943634). By single locus analysis, no differences in genotype distribution and allelic frequency were found between the two groups of study. The risk allele (C) for rs2943634 was less frequent among Tunisian population than in controls from the WTCCC and German studies (57% vs 65%). The three SNPs previously reported to be associated with CHD were not replicated in our small sample.
Assuntos
Aminoidrolases/genética , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 9 , Doença das Coronárias/genética , Formiato-Tetra-Hidrofolato Ligase/genética , Estudo de Associação Genômica Ampla , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Idoso , Estudos de Casos e Controles , Feminino , Genoma , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , TunísiaRESUMO
BACKGROUND: Recent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Several lines of evidence support a key role for tumor necrosis factor-alpha (TNF-alpha), a potent immunomodulator and pro-inflammatory cytokine, in the development of atherosclerosis and in complications of CAD. METHODS: We investigated the possible association between CAD and the TNF gene promoter polymorphisms -308G>A and -1031T>C in a Tunisian population. We compared the distribution of these polymorphisms between 418 patients with CAD and 406 healthy controls using polymerase chain reaction restriction fragment length-polymorphism analysis. RESULTS: The frequency of the TNF-alpha -308A allele in the control group was similar to that observed in CAD patients [p=0.78; odds ratio (OR)=1.15; 95% confidence interval (CI)=0.86-1.55], but higher than those described in other Europeans, such as in the French, Finnish and Spanish. Concerning the TNF-alpha -1031T/C polymorphism, the same distribution was observed between patients with CAD and controls (p=0.12; OR=1.27; 95% CI=0.94-1.72). In addition, the genotype and allele frequencies of control individuals were comparable to those previously reported in healthy Tunisian controls and other ethnic groups. Haplotype analysis (TNF-alpha -308G>A and -1031T>C) demonstrated no significant association between TNF haplotypes and CAD. CONCLUSIONS: We conclude that TNF promoter gene polymorphisms at position -308G>A and -1031T>C do not play a major role in the pathogenesis of CAD in the Tunisian population.
