CYP19A1, also known as aromatase, is an important enzyme that produces estrogen. By controlling estrogen levels, CYP19A1 affects a variety of processes in the body, including fat production and distribution, bone density, female fertility, and brain function. Estrogen deficiency is associated with diseases such as osteoporosis, hardening of the arteries, and Alzheimer’s. Furthermore, CYP19A1 gene variants have been associated with migraines and the growth of estrogen-sensitive cancers. In this post, you will find information about aromatase function, gene variants, and factors that may affect its activity.
What is CYP19A1?
Aromatase (CYP19A1) is one of the cytochrome P450 monooxygenases (CYPs) [1].
Many CYPs eliminate toxins and drugs from the human body. However, some, like CYP19A1, are not involved in detoxification but in steroid hormone production.
Function
Aromatase is a key enzyme in estrogen production. It converts androstenedione and testosterone to estrone and estradiol, respectively [2].
Location
This enzyme is found in the ovaries, placenta, testis, fat tissue, brain, liver, muscles, and hair follicles [3, 4, 5].
The Good
By controlling estrogen production, CYP19A1 affects a variety of processes in the body, such as:
Estrogen deficiency has been associated with a variety of diseases, including osteoporosis, hardening of the arteries (atherosclerosis), and Alzheimer’s disease [10].
CYP19A1 is also involved in the sexual development of the brain [9]. How the brain develops and functions depends on the levels of sex hormones it is exposed to.
Furthermore, CYP19A1 also affects cognitive function. It is implicated in reading, speech, and language [9]. Studies suggest estrogen has important roles in learning and memory by enhancing neuron structure and function [9].
Mutations in CYP19A1 have been associated with dyslexia (a study in 3423 subjects) [9].
The Bad
Increased aromatase activity, resulting in higher estrogen, can promote the growth of estrogen-sensitive cancers.
Gene Polymorphisms
To date, hundreds of CYP19A1 variants have been identified [11].
However, complete CYP19A1 enzyme deficiency is very rare. To date, only 24 cases have been reported worldwide [9, 12].
Clinical features of CYP19A1 deficiency include:
- maternal virilization in pregnancy (male-pattern hair growth and other masculine physical traits) due to the excess of androgens and lack of estrogens coming from the fetus. These resolve gradually after giving birth [12].
- (in women) virilized external genitalia, hemorrhagic ovarian cysts in childhood, primary amenorrhea (absence of menstruation), no breast development, and decreased bone density [12].
- (in men) osteoporosis due to impaired bone mineralization. Also may have abnormal testis size and sperm production, metabolic syndrome-like stomach obesity, and insulin resistance [12].
RS10046
Studies have found that having rs10046 ‘T’ variant increases CYP19A1 levels (resulting in more estrogen) [5].
Two studies in 2250 and 443 subjects, respectively, have found that the ‘TT’ genotype may contribute to hypertension (elevated blood pressure) [6, 13].
In a study of 283 people ‘TT’ genotype was also associated with migraine susceptibility [14].
On the other hand, ‘CC’ genotype has been associated with higher apo B, insulin, BMI, and HOMA index (2250 subjects) [6].
A small study with 189 people has found a link between the ‘C’ variant may also be more prone to heart disease [15].
RS1004982
A study has found a link between rs1004982 ‘CC’ genotype and breast cancer (1958 women) [16].
RS1004984
A study in 1241 people found that rs1902584 ‘A’ carrier women tend to have a higher waist-to-hip ratio i.e. they may be more prone to obesity [17].
RS17703883
Among 2392 men, ‘C’ carriers (those with either ‘TC’ or ‘CC’ genotypes) had 1.5 times higher odds of having a low bone mineral density [7].
RS1902584
rs1902584 ‘T’ carrier women tended to have a higher waist-to-hip ratio i.e. they are more prone to obesity (a study of 1241 people) [17].
RS2470144
Having rs2470144 ‘AA’ genotype was associated with a lower likelihood of having rectal cancer (791 cases and 999 controls) [18].
RS28566535
In 1958 women, rs28566535 ‘CC’ genotype was associated with greater likelyhood of having breast cancer [16].
RS2899470
‘T’ carriers were more likely to have endometriosis, according to a study with 262 patients and 275 controls [19].
RS4646
A study suggests that the common rs4646 ‘C’ variant increases estrogen levels and may predispose women to female pattern hair loss (955 subjects) [20].
On the other hand, the ‘T’ variant for the rs4646 was associated with an advanced stage of breast cancer at the time of presentation and a more progressive disease in another study of 327 patients [21].
RS4775936
In one study, woman ‘AA’ carriers tended to have a higher bone mineral density (256 subjects) [22].
In another study, having rs4775936 ‘GG’ genotype was associated with breast cancer (1958 subjects) [16].
Interestingly, blood pressure was higher in men but lower in women with the ‘GG’ genotype (218 patients and 225 controls) [13]. Another study confirmed that women ‘A’ carriers tend to have higher blood pressure (639 people) [23].
RS700519
This variant has been associated with endometrial cancer (1,040 patients and 1,031 controls) [2, 24].
In another study, women with rs700519 ‘TT’ genotype had lower breast cancer survival rates (1,136 women) [25].
RS727479
The ‘C’ variant produces 10-20% more estrogen in postmenopausal women [26].
A study suggests that rs727479 ‘C’ may be linked with lung cancer (529 patients and 567 controls) [27].
Carrying an ‘A’, on the other hand, has been associated with endometrial cancer (10 studies, 4,998 cases, and 8,285 controls) [28].
RS749292
rs749292 produces 10-20% more estrogen in postmenopausal women [26].
The ‘A’ variant has been associated with endometrial cancer (10 studies, 4,998 cases, and 8,285 controls) and ovarian cancer (367 cases and 602 controls) [28, 26].
RS936306
rs936306 ‘TT’ had been associated with breast cancer (1958 women) [16].
RS700158
One study in 286 women has found a link between rs700158 ‘G’ variant and preeclampsia (a pregnancy complication) [29].
RS11632903 and RS1902586
rs11632903 and rs1902586 have been moderately associated with dyslexia in a study of 3423 people [9].
RS3751592
‘G’ in rs3751592 was associated with Alzheimer’s disease in a study of 463 people [11].
RS11575899
This variant (del/del) has been associated with melanoma (117 cases and 116 controls) [30].
Important Limitations
Remember, these SNPs have only been found to be associated with certain health conditions. In other words, we only have one or two association studies suggesting that certain genetic variants are more common in people with certain conditions. However, more research will be needed to know what role, if any, these variants play in actually causing these conditions.
In addition, many of these conditions are complex and affected by a multitude of factors, including your lifestyle choices, and CYP19A1 may only play a small part.
Therefore, just because you have one of these SNPs or genotypes does not necessarily mean you are at an increased risk of developing any of these conditions.
Increasing or Decreasing CYP19A1
These increase CYP19A1 in Humans:
- Dichlorodiphenyl ethylene (DDE, derived from DDT) [31]
These increase CYP19A1 in Cells:
These decrease CYP19A1 in Animals and Cells:
- Olive tree leaves [33] and olive oil [34]
- Curcumin [35]
- Apigenin [36]
- Naringenin [36]
- Hesperetin [36]
- Chrysin [37]
- Kaempferol [38]
- Capsaicin [39]
- Mango peel [33]
- Lemons and limonoids found in lemons [40]
- Mangosteen [41]
- Ginkgo biloba [42, 43]
- Sumac sorghum bran extract [44]
- Licorice flavonoid isoliquiritigenin [45, 46]
- Biochanin A, from red clover (Trifolium pratense) [47]
- Hop flavonoids xanthohumol, isoxanthohumol, and 8-prenylnaringenin [48, 49]
- Lager beer, alcohol-free beer, stout beer, and xanthohumol-rich stout beer [49]
- Red wine [37, 41]
- Grape seed extract [50, 41]
- Tea [37, 41]
- Coffee [41]
- Cocoa [41]
- Collards (including cabbage and broccoli) [41]
- Tomato leaves [41]
- Stinging nettle root extract [51]
- Cigarette smoke and tobacco leaves [41]
- White button mushroom unsaturated fatty acids [52]
- Damiana (Turnera diffusa) [53]
These may both increase and decrease CYP19A1 in Cells:
It’s important to stress that what’s found in cell and animal studies, doesn’t always match what’s later found in humans. The findings from animal and cell studies are given solely for information purposes and will be updated as soon as new findings from human studies become available.
