DHFR and triple-A syndrome: In 2019, Prestel, M et al. founding that allele-specific transcriptional regulation of HDAC9 via E2F3 and RB1 as a major mechanism mediating vascular risk at rs2107595 [17]; but Yu Cao et al. another findings reveals that endothelial RB positively impacts arterial function by supporting vasoprotective endothelial DHFR/NO pathway activity, leading to reduced abdominal aortic aneurysm (AAA) development [18], their results are inconsistent.