A Potential Role for Aromatase Levels in Coronary Heart Disease

This month's highlight article in Genetic Testing and Molecular Biomarkers is Identification of a CYP19 gene single-nucleotide polymorphism associated with reduced risk of coronary heart disease, by Wang et al. (2016). It provides crucial insight into the mechanism underlying the long-known phenomenon that premenopausal women are partially protected from coronary heart disease (CHD) compared with their same-age male counterparts and their postmenopausal sistren. This difference in risk was originally determined epidemiologically, wherein it was shown at the population level that it was only some years after the onset of menopause that women develop CHD risk similar to men. This observation has led to the belief that there exists a protective estrogenic effect against CHD, which has been supported, in part, by the observation that late menopause further delays an increased risk of CHD among women.

Wang et al. (2016) have now demonstrated in a case-control study, using propensity score matching to minimize covariate risks, that a single-nucleotide polymorphism in the CYP19 gene when present only in heterozygotes may reduce the risk of CHD. This is potentially mechanistically important as the CYP19 gene has been previously shown to encode the aromatase enzyme that is responsible for the conversion of testosterone to estradiol. Interestingly, previous studies have indicated that one of the major anatomic sites of aromatase production is in the great vessels of the heart. These data fit with earlier reports that have suggested that it is the testosterone/estradiol ratios that are important for coronary health and that both CYP19 mutations that affect aromatase levels and aromatase inhibitors might be associated with increased CHD levels.

Clearly, further studies are needed as the authors did not collect aromatase levels, nor androgen/estrogen levels from their study subjects. Moreover, it will be important to learn why the heterozygous form, but not the homozygous form of the minor allele, appears to be protective. The possibility, however, that it is the androgen/estrogen ratio that is protective of CHD, rather than the absolute levels of either may provide a clue.