AUTHOR=Lv Yuanyuan , Zhao Wenying , Yu Laikang , Yu Ji-Guo , Zhao Li 

TITLE=Angiotensin-Converting Enzyme Gene D/I Polymorphism in Relation to Endothelial Function and Endothelial-Released Factors in Chinese Women

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00951

DOI=10.3389/fphys.2020.00951

ISSN=1664-042X

ABSTRACT=<p>Many studies have investigated the relationship between angiotensin-converting enzyme (<italic>ACE</italic>) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect to <italic>ACE</italic> D/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22–75 years) were enrolled and divided into pre-menopause group and post-menopause group. After <italic>ACE</italic> D/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies of <italic>ACE</italic> D/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD (<italic>P</italic> = 0.032), and age-dependent in both genotypes (DD, <italic>P</italic> = 0.0472; DI/II, <italic>P</italic> &lt; 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II (<italic>P</italic> &lt; 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II (<italic>P</italic> = 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO, <italic>P</italic> = 0.032; ET-1, <italic>P</italic> = 0.017; Ang II, <italic>P</italic> = 0.002), but only with Ang II in women of DI/II (<italic>P</italic> = 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD (<italic>P</italic> = 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease.</p>