Association of prothrombin, FV Leiden and MTHFR gene polymorphisms in the Montenegrin patients with venous thromboembolism

Abstract

Background / Aim. Polymorphisms of the factor V Leiden (FV G1691A), factor II Prothrombin (FII G20210A) and methylenetetrahydrofolate reductase (MTHFR C677T) genes are the most commonly investigated inherited risk factors for developing venous thromboembolism (VTE). Despite this fact, there is insufficient data regarding their clinical burden and distribution in Montenegrin population. Consequently, the present study aimed to determine the frequency of these polymorphisms in Montenegrin patients with VTE. Methods. This case-control study was conducted on 160Caucasian subjects. The study group was composed of 80 patients (35 men and 45 women) with VTE. The control group consisted of 80 healthy individuals (32 men and 48 women), without previous thromboembolic episode. Genotyping of the FV G1691A, FII G20210A, and MTHFR C677T polymorphisms was performed by allele-specific polymerase chain reaction (PCR). Results. Our results demonstrated that the frequency of heterozygotes (HET) for FII G20210A and FV G1691A were significantly higher in VTE group compared to a healthy control group (χ2 = 11.7; p = 0.001 and χ2 = 17.69; p < 0.001respectively). This study confirmed the association of FII G20210A and FV G1691A polymorphisms with an increased risk of VTE (OR 10.5; 95 % CI = 2.34 to 47.27 and OR 14.8; 95 % CI = 3.34 to 65.43; p < 0.001respectively). Recessive homozygotes (RH) for FII G20210A and FV G1691A were not found in any of investigated group. As regarding MTHFR C677T, the difference between the frequency of HET and RH in the control and VTE group is not significant. Conclusion. Our study has shown that FII G20210A and FV G1691A polymorphisms are significantly associated with the VTE. Detection of above mentioned polymorphisms prior to VTE development can contribute to the prevention of further VTE occurrence, especially among patients' relatives who are carriers of these polymorphisms. Key words: venous thromboembolism, gene polymorphisms, FII G20210A, FV G1691А, MTHFR C677T. Apstrakt Uvod / Cilj. Polimorfizmi u genima koji kodiraju faktor V Leiden (FV G1691A), faktor II Protrombin (FII G20210A) i metilen tetrahidrofolat reduktazu (MTHFR C677T) su najčešće ispitivani nasledni faktori rizika za nastanak venskog tromboembolizma (VTE). Uprkos tome ne postoji dovoljno podataka o kliničkom značaju i distribuciji ovih polimorfizama u crnogorskoj populaciji. U skladu sa tim, cilj ove studije bio je da utvrdi frekvenciju ovih polimorfizama kod pacijenta sa venskim tromboembolizmom u Crnoj Gori. Metode. Studija: slučaj-kontrola. Istraživanje je sprovedeno na 160 ispitanika Kavkaskog porekla. Studijsku grupu sačinjavalo je 80 pacijenata (35 muškaraca i 45 žena) sa VTE, a kontrolna grupa se sastojala od 80 zdravih ispitanika (32 muškarca i 48 žena), koji nisu imali tromboembolijske epizode bolesti. Genotipizacija polimorfizama za: FV G1691A, FII G20210A i MTHFR C677T izvršena je alel specifičnom, lančanom reakcijom polimeraze. Rezultati. Rezultati ove studije su pokazali da je učestalost heterozigota (HET) za FII G20210A i ...

Polymorphisms ofACEand thrombophilic genes: risk for recurrent pregnancy loss

“…Our study showed that the prevalence of heterozygous F2 20 210G>A and F5 1691G>A polymorphisms in the control fertile population of Montenegrin women was lower (1.1% and 2.1%, respectively) than it was found for the European – Caucasian population, but it was in the range of reported results within different populations. We previously reported a similar prevalence for F2 and F5 heterozygotes (both 2.5%) in the general Montenegrin population,18 but neither the present, nor our previous study showed the presence of variant homozygotes in these genes among general population. The prevalence of F2 20 210G>A and F5 1691G>A heterozygotes among women with RPL and IUFD in our study was lower than reported in the studies that confirmed the association between these polymorphisms and early/late RPL and late non-recurrent PL and IUFD 9 10 19–21.…”