A1298C polymorphism in the MTHFR gene

Thrombophilia is a tendency to increased blood clotting, which is influenced by both congenital predisposition and external influences (e.g. exercise regimen, weight, age, smoking, trauma, medication). People with higher blood coagulability are at greater risk of blood clots (thrombi), which can lead to partial or complete closure of blood vessels – most often in deep veins of the lower limbs (deep vein thrombosis). Some of the clot can break free, travel through the venous system and close one of the pulmonary vessels after passing through the heart, i.e. development of a pulmonary embolism. Placental thrombosis can compromise the course of pregnancy. External stimuli for the formation of blood clots include hormonal contraception, hormonal treatment of infertility or pregnancy. 

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is the main form of folate in the body. Folates act as monocarbon donors for many metabolic reactions, including homocysteine methylation and synthesis nucleotides, protein neurotransmitters and phospholipids. The incidence of these polymorphisms in the population is up to 40%. The homocysteine level is also affected by many other influences, especially the intake of folic acid, vitamin B12 and B6. Pregnant women with a MTHFR gene mutation have been shown to have a higher risk of cleft defects in the foetus (gastroschisis or spina bifida). As a precaution, the use of folic acid and B vitamins is recommended at higher doses (up to 20 times) compared to the general population 3 months before planned pregnancy and in the first 3 months of pregnancy. 

Heterozygous findings without concurrent evidence of hyperhomocysteinemia tend to be clinically insignificant. This is a common finding (in about 30% of the population). 

Homozygous findings are associated with mild to moderate hyperhomocysteinemia (regular determination of homocysteine levels is recommended).

Before initiating combined oral hormonal contraception and/or hormone replacement therapy (HRT) in women with a positive personal history of TEN or a positive family history of TEN in first-degree relatives (mother, father, siblings and children), in women with primary sterility or recurrent abortions in the first trimester of pregnancy or in any foetal loss after this period of gestation, in pregnant women with a positive personal or family history of TEN (see Section 1) or in severe forms of preeclampsia, foetal retardation, placental abruption and stillbirth, in persons with a history of idiopathic TEN to determine the causative cause and to decide on the duration of anticoagulant therapy. If thrombophilic mutations are positively detected, it is advisable to perform these tests in first-degree relatives. In children older than 12 years, unless there are other reasons to perform this testing sooner, or from another indication after examination in the Thrombotic Centre, or indications are part of the Recommended Practice of the Society for Medical Genetics and Genomics, J. E. Purkyne Czech Medical Society – see https://slg.cz/doporuceni/trombofilni-stavy/