Cyp19a1, also known as aromatase, is a member of the cytochrome P450 family of heme-thiolate monooxygenases. It is located in the endoplasmic reticulum and plays a major role in converting androgens into estrogens, which is essential for female sexual development as well as growth and development in both sexes. The gene is part of the steroid biosynthesis pathway, and its activity depends on reducing equivalents from the reduced nicotinamide adenine dinucleotide phosphate via the cytochrome P450 oxidoreductase coded by POR [3].

In a Chinese Han population study, the contribution of CYP19A1 polymorphisms to coronary heart disease (CHD) susceptibility was found to be associated with age, gender, and clinical phenotypes. The study suggested that CYP19A1 polymorphisms might play a role in the incidence of CHD [1]. A case-control study and meta-analysis in China indicated that the CYP19A1 rs700519 polymorphism is related to breast tumorigenesis, with the rs700519 AA genotype showing a negative relationship with breast cancer risk and disease-free survival rates, especially in postmenopausal hormone receptor-positive patients [2]. Research on the differential effects of variations in human P450 oxidoreductase on CYP19A1 polymorphisms R264C and R264H revealed that allelic variants of P450 when present with a variant form of POR may show different aromatase activities, emphasizing the importance of considering combined gene variations [3]. A study on pregnant women using selective serotonin reuptake inhibitors (SSRIs) showed that SSRI use altered placental CYP19A1 enzyme activity, which may lead to disturbances in maternal steroid hormone balance [4]. In women with endometriosis, although there was no difference in CYP19A1 mRNA expression in luteinized granulosa cells compared to controls, the correlation between CYP19A1 expression and follicular estradiol levels and the number of oocytes retrieved was different from that in the control group, suggesting a potential subtle mechanism affecting the ovulation process [5].

In conclusion, Cyp19a1 is crucial for estrogen synthesis and is involved in multiple biological processes. Studies on CYP19A1 polymorphisms and its enzyme activity variations have provided insights into its role in diseases such as coronary heart disease, breast cancer, and in the context of pregnancy and endometriosis. These findings contribute to a better understanding of the biological functions of Cyp19a1 and its implications in various disease conditions.

References:

1. Ye, Wei, Tang, Qizhu, Wang, Lei, He, Qi, Peng, Kaiwei. 2022. Contribution of CYP19A1, CYP1A1, and CYP1A2 polymorphisms in coronary heart disease risk among the Chinese Han population. In Functional & integrative genomics, 22, 515-524. doi:10.1007/s10142-022-00850-y. https://pubmed.ncbi.nlm.nih.gov/35380334/

2. Lv, Fei, Huang, Wanying, Wang, Ying. . The CYP19A1 rs700519 Polymorphism and Breast Cancer Susceptibility in China: A Case-Control Study and Updated Meta-Analysis. In Genetic testing and molecular biomarkers, 25, 486-495. doi:10.1089/gtmb.2021.0032. https://pubmed.ncbi.nlm.nih.gov/34280004/

3. Parween, Shaheena, DiNardo, Giovanna, Baj, Francesca, Gilardi, Gianfranco, Pandey, Amit V. 2019. Differential effects of variations in human P450 oxidoreductase on the aromatase activity of CYP19A1 polymorphisms R264C and R264H. In The Journal of steroid biochemistry and molecular biology, 196, 105507. doi:10.1016/j.jsbmb.2019.105507. https://pubmed.ncbi.nlm.nih.gov/31669572/

4. Sahlman, H, Itkonen, A, Lehtonen, M, Keski-Nisula, L, Rysä, J. 2022. Altered activities of CYP1A1 and CYP19A1 enzymes in women using SSRI medication during pregnancy. In Placenta, 129, 30-35. doi:10.1016/j.placenta.2022.09.013. https://pubmed.ncbi.nlm.nih.gov/36198245/

5. Giacomini, Elisa, Pagliardini, Luca, Minetto, Sabrina, Somigliana, Edgardo, Viganò, Paola. 2023. The relationship between CYP19A1 gene expression in luteinized granulosa cells and follicular estradiol output in women with endometriosis. In The Journal of steroid biochemistry and molecular biology, 237, 106439. doi:10.1016/j.jsbmb.2023.106439. https://pubmed.ncbi.nlm.nih.gov/38048918/