Association of coagulation - related genes polymorphism with deep venous thrombosis and pulmonary embolism

[S. D. Teofilov]

145, [3] листа

Venska tromboza (VTE) je patološka koagulacija, u čijem nastanku genetički faktori rizika imaju značajnu ulogu. Glavni cilj studije je da utvrdi da li su polimorfizmi jednog nukleotida (SNP) gena koji kodiraju faktore koagulacije, i to: FVHR26755A>G, FII19911A>G, FXIII-A102G>T, MTHFR677C>T, PAI14G/5G i FSAP1601G>A, povezani sa nastankom, karakteristikama i recidivom VTE. U studiju su uključena 103 pacijenta, koji su na osnovu važećih dijagnostičkih algoritama imali bar jednu trombozu i 106 kontrola, koji do trenutka kada su prihvatili učešće u studiji nisu imali trombozu. Genotipizacija je sprovedena metodom alel- specifičnog PCR. Među SNPs FV1691G>A i FVHR26775A>G je uočen umeren LD, a među SNPs FII20210G>A i FII19911A>G kompletan LD. Multivarijantnom analizom uticaja svih ispitivanih SNPs na rizik od tromboze, pored potvrđenog višestrukog rizika za nosioce FII20210G>A i FV1691G>A, pokazan je skoro trostruko povećan rizik kod nosioca FVHR26755A>G (p=0,024; OR=2,89). U okviru ukupnog uticaja svih ispitivanih SNPs, prisustvo varijantnog genotipa FXIII-A102G>T udruženo je sa skoro dva i po puta manjim rizikom od razvoja VTE. U udruženom dejstvu genotipova svih SNPs i ostalih ispitivanih faktora rizika za VTE, prisustvo bar jednog varijantnog MTHFR677T alela povezano je sa skoro trostruko većim rizikom od nastanka VTE. Varijantni genotipovi na 4 i više gena, češće su zastupljeni kod VTE pacijenata (p=0,007) kao i kod pacijenata mlađih od 50 godina u odnosu na kontrole iste starosti (p=0,02). Prisustvo varijantnih formi do sada nedovoljno ispitanog haplotipa FV HR26775A>G u zajedničkom uticaju svih ispitivanih SNPs, kao i MTHFR677C>T, u zajedničkom uticaju SNPs i ispitivanih stečenih faktora rizika. doprinose povećanom riziku od VTE.

Venous thrombosis (VTE) is a pathological coagulation, in whose etiopathogenesis genetic risk factors play a significant role. The main objective of this study was to determine if single nucleotide polymorphisms (SNP) of genes encoding coagulation factors, namely: FVHR26755A>G, FII19911A>G, FXIII-A102G>T, MTHFR677C>T, PAI14G/5G and FSAP1601G>A, are associated with the onset, characteristics, and recurrence of VTE. The study included 103 patients, who, based on valid diagnostic algorithms, had at least one confirmed thrombosis, and 106 healthy subjects, who had no thrombosis until the moment they accepted to participate in the study. Genotyping was carried out by allele-specific PCR method. There was a moderate LD observed between FV1691G>A and FVHR26775A>G polymorphisms, while complete LD was observed between polymorphisms FII20210G>A and FII19911A>G. Multivariate analysis of the influence of all examined SNPs on the risk of thrombosis, in addition to the confirmed multiple risk for FII 20210G>A and FV 1691G>A carriers, showed an almost three-fold increased risk in FVHR26755A>G carriers (p=0.024; OR=2.89).Within the overall influence of all examined SNPs, the presence of the FXIII-A102G>T variant genotype was associated with an almost two and a half times lower risk of developing VTE. Within the combined effect of all analyzed SNPs and other examined risk factors for VTE, the presence of at least one variant MTHFR 677T allele was associated with an almost three-fold higher risk of VTE.Variant genotypes on 4 or more genes are more common in VTE patients (p=0.007), as well as in patients younger than 50 years, as compared to healthy subjects of the same age (p=0.02). The presence of variant forms of the hitherto insufficiently investigated haplotype FVHR26775A>G in the joint influence of all investigated SNPs, as well as MTHFR677C>T in the joint influence of SNPs and the examined acquired risk factors. contribute to an increased risk of VTE.

VTE, SNP, faktori koagulacije

VTE, SNP, coagulation factors

575:616.1(043.3)

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