Mutations in the prothrombin gene, known as factor II mutations, are genetically related, so they are acquired through inheritance. This gene is responsible for producing prothrombin, which is converted into thrombin in vivo, so this defect is sometimes known as a thrombin gene mutation. Thrombin, in turn, converts the water-soluble fibrinogen into an insoluble molecule, fibrin, which is an essential component of the blood clotting mechanism. Thrombin gene mutations are the second-largest risk factor for developing thrombosis, or deep blood clots inside of blood vessels, next to the factor V mutation.
A thrombin gene mutation is congenital, so a person can have either one or two copies of the mutated gene, with two copies putting the individual at a far greater risk of thrombosis. Thrombin gene mutation is an autosomal dominant mutation, meaning that a person with one copy of the mutation has a 50 percent chance of passing it on to his or her children. Both males and females, as well as persons of any blood type, are at equal risk of inheriting this gene and having an associated risk of thrombosis if they do.
This mutation is not generally inherited with other mutations, and it involves a point mutation at position 20210 on the prothrombin gene, located on the 11th chromosome. About 1-2 percent of the Caucasian population is heterozygous for the factor II mutation, meaning that those people have one copy of the defective gene. The prevalence rate is far lower in people of other racial backgrounds.
When this mutation is inherited, it slows the degradation of prothrombin messenger RNA, thus increasing prothrombin production, which leads to a greater amount of thrombin in the blood. In turn, the clotting process can occur much more easily because of the excess thrombin becoming involved in a cascade of fibrin creation, which can end in thrombosis. The thrombin gene mutation increases the risk of deep vein thrombosis by about two to three times. There are also other health risks from the elevated levels of thrombin, particularly recurrent miscarriage.
Thrombin gene mutation increases the risk of thrombosis, but it does not necessarily mean that a person will develop this disorder. There are other risk factors that can increase the chances of thrombosis, particularly with a mutated copy of the gene. These risk factors include the use of oral contraceptives, inheriting another genetic mutation known as factor V mutation, becoming pregnant, smoking cigarettes, obesity or remaining immobile for long periods of time.