RESUMO
BACKGROUND: To investigate possible associations of P-selectin polymorphisms with idiopathic recurrent pregnancy loss (RPL). METHODS: Study subjects comprised 270 consecutive RPL cases attending outpatient maternity services, and 322 multi-parous control women. P-selectin genotyping was done by PCR-RFLP and PCR-ASA methods. RESULTS: The P-selectin variants rs1800807, rs1800805, and rs6127, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs6127 A allele (P<0.001I), but not rs1800807 C allele (P=0.957) or rs1800805 A allele (P=0.760), was higher in RPL cases than in control women. Significant differences in the distribution of rs6127 (P<0.001), but not rs1800807 (P=0.444) or rs1800805 (P=0.391) genotypes were seen between cases and controls, and only rs6127 showed a significant association with RPL, with increments of 2.65 and 4.96 in disease risk seen for heterozygous and homozygous carriers, respectively. Among the 8 three-locus Pselectin haplotypes constructed (rs1800807/rs1800805/rs6127), increased frequency of GGG (Pc=0.0249), CGG (Pc=0.0256), and CAG (Pc=0.0174) haplotypes, and lower frequency of CGA haplotype (Pc=0.0091) were seen in RPL cases, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. CONCLUSIONS: P-selectin gene polymorphisms and haplotypes contribute to RPL development.
Assuntos
Aborto Espontâneo/genética , Selectina-P/genética , Polimorfismo Genético , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Gravidez , Complicações na Gravidez/genéticaRESUMO
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
OBJECTIVE: Our aim was to evaluate the contribution of tumor necrosis factor (TNF)-alpha -308G>A and interleukin (IL)-6 -174G>C gene promoter variants to the presence of coronary artery disease (CAD) in Tunisians. DESIGN AND METHODS: Study subjects comprised 418 angiographically proven CAD patients and 406 age-, gender-, and ethnic origin-matched controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: There were no significant differences in the allelic distribution of TNF-alpha -308A (19.6% vs. 19.0%, P=0.73), and IL-6 -174C (15.6% vs. 14.3%, P=0.47) promoter polymorphisms between CAD patients and control subjects, respectively. In addition, single locus analysis revealed no differences in genotype frequencies between the two study groups, and the combined distribution of both genotypes did not differ significantly between controls and CAD patients (P>0.05). CONCLUSION: There is no allelic or genotypic association of TNF-alpha -308G>A and IL-6 -174G>C promoter polymorphisms with CAD in Tunisians, thereby confirming an ethnic-selective contribution of both gene variants to CAD presence.
