What is CYP21A2?
This enzyme is also known as 21-hydroxylase. It is one of the cytochrome P450 monooxygenase enzymes (CYPs) .
Many CYP enzymes eliminate toxins and drugs from the human body. However, some, like CYP21A2, are not involved in the detox process. Instead, they produce steroid hormones.
This enzyme is responsible for cortisol production .
Cortisol is produced in response to stress. It increases energy but suppresses the immune system.
CYP21A2 also helps produce aldosterone .
Aldosterone helps our bodies conserve sodium and maintain blood pressure.
CYP21A2 Gene Polymorphism
The CYP21A2 gene has over 35 variants . More are discovered by the day.
There are some people who don’t have this gene or those who have more than two gene copies .
Most of the mutations decrease the activity of this enzyme. Lower enzyme activity, in turn, decreases aldosterone and cortisol levels but increases testosterone .
Complete Enzyme Deficiency
In most of the cases, a complete lack of the enzyme causes congenital adrenal hyperplasia . Common symptoms of this dissease are:
- virilizing effects. Women develop male-pattern hair growth and other masculine traits .
- salt-wasting (low blood sodium due to aldosterone deficiency) .
- oligomenorrhea or amenorrhea (infrequent or absent menstruation) .
- polycystic ovaries .
- ambiguous genitalia in girls .
Mutations that cause a total lack of enzyme function are rare (1 in about 15,000).
Mild Enzyme Deficiency
Mutations that cause mild enzyme deficiency are much more common.
They occur in 1 in 100 subjects. They can be even more frequent in some populations, such as Eastern European Jews (1 in 27) .
These people retain ∼20-60% enzyme activity .
- Excessive body hair, infrequent menstrual periods, and impaired fertility in women .
- Short stature and low fertility in adult men, due to the excess of androgens .
Why are CYP21A2 mutations so frequent?
Mutations in this gene may confer an advantage, as a result of the higher activity of the hypothalamic-pituitary-adrenal axis (HPA axis) . This axis controls many processes, including the response to stress, mood and emotions.
Mutation carriers have a lower risk of developing mood and stress-related disorders. They are less often diagnosed with psychiatric disorders. Also, they are less vulnerable to mentally stressful situations (over 600 patients) .
These decrease CYP21A2:
- 1α,25-dihydroxyvitamin D(3), derived from vitamin D .