Predictive role of MTHFR, FGB, F2 and F5 genes polymorphisms in the development of pulmonary embolism

Aim. Research the relationship of gene polymorphisms (MTHFR, FGB, F2, F5) with the development of pulmonary embolism (PE).

Material and methods. The study involved 120 people (main group) who underwent PE. Mean age is 63.22±3.16 years (66 men, mean age 60.24±3.17 years; 54 women, mean age 66.19±3.67 years). The control group was composed of Research Institute of Internal and Preventive medicine (Novosibirsk) DNA bank (comparable to the main group by gender and age). This DNA bank was formed during a series of population-based screening. The material for the study includes whole blood, plasma and serum samples, DNA samples, as well as medical records of patients undergoing PE. DNA extraction from venous blood was performed by the phenol-chloroform method. FGA (Del/Ins) rs35496957 was genotyped using polymerase chain reaction (PCR) with flanking primers-8202 A/G, rs11697325 mmp9 – using PCR with RFLP. Polymorphisms of genes MTHFR, FGB, F2, F5 were tested by real-time PCR on test systems produced by DNA-technology (Russia) on a DTPrime device (Russia). For structuring and statistical data processing Microsoft Excel and the Microsoft Office software package and the STATISTICA (USA) software package for statistical analysis were used. The study includes the calculation of the following output data and parameters based on the collected incoming statistical data: standard deviation, calculating the mean square value, Pearson's chi-square, likelihood ratios, Fisher's exact test and linear-by-linear association.

Results. It was found that the odds ratio of developing PE in men carriers of the TT genotype of the C677T polymorphism of the MTHFR gene at the age of 65 years and older was 4.43 times higher than in carriers of the other two genotypes (95% confidence interval 1.33–14.73; p=0.019). There was a tendency of more frequent detection of the genotype GG polymorphism rs1800790 (-455 G>A) of the FGB gene among men individuals of the main group compared with the control group (63.6 and 54.0%, respectively). There was also a decrease in the number of respondents with the AA genotype of the rs1800790 polymorphism (-455 G>A) of the FGB gene in the group of both genders. There was a tendency of more frequent PE cases among women individuals with genotype GG and GA of the rs1799963 polymorphism of the F2 gene in the main group (85.20 and 14.80%, respectively).

Conclusion. Further research of genetic factors’ role in the occurrence of PE is extremely important for clinical practice taking into consideration the possibility of developing a personalized approach to treatment and prevention of the diseases related to disorders in the hemostatic system.