RESUMO
Objective To study the association of polymorphisms rs699947, rs2010963, rs3025039 in the VEGFA gene region and rs1870377, rs2305949, rs2071559 in the VEGFR2 gene region with the risk of primary varicose veins in ethnic Russians. Methods Genotypes were determined by real-time PCR allelic discrimination. The case group consisted of 448 patients with primary varicose veins and the control group comprised 609 individuals without a history of chronic venous disease. Association was studied by logistic regression analysis. Results Allele rs2010963 C was associated with the decreased risk of varicose veins (additive model of inheritance: odds ratio = 0.73, 95% confidence interval = 0.59-0.91, P = 0.004). Conclusions Our results provide evidence that polymorphism rs2010963 located in the 5' untranslated region of the VEGFA gene can influence genetic susceptibility to primary varicose veins in Russians. Otherwise, it can be in linkage disequilibrium with another functional single nucleotide polymorphism that can alter the level of vascular endothelial growth factor A protein.
Assuntos
Polimorfismo de Nucleotídeo Único , Varizes/genética , Fator A de Crescimento do Endotélio Vascular/genética , Regiões 5' não Traduzidas , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Proteção , Fatores de Risco , Federação Russa/epidemiologia , Varizes/diagnóstico , Varizes/etnologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto JovemRESUMO
Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.
Assuntos
Substituição de Aminoácidos , Predisposição Genética para Doença , Proteína da Hemocromatose/genética , Polimorfismo Genético , Varizes/genética , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Genes , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa , Adulto JovemRESUMO
OBJECTIVE: To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians. METHODS: Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease. RESULTS: Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C-rs4633732 T-rs34221221 C-rs1035550 C-rs34152738 T-rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01). CONCLUSIONS: Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.