Angiotensin converting enzyme intron 16 insertion/deletion genotype is associated with plasma C-reactive protein concentration in uteroplacental dysfunction

Abstract

Introduction: Disturbance of the uteroplacental circulation (UPC) and the renin-angiotensin system are involved in the pathogenesis of preeclampsia. In women with history of preeclampsia persistently elevated C-reactive protein (CRP) levels have been described. The angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) genotype is associated with ACE activity and assumed to be a risk factor for preeclampsia. As ACE generates proinflammatory angiotensin II, we analysed, whether ACE intron 16 I/D genotype is associated with CRP and whether this association exhibited a relation to uteroplacental dysfunction. Materials and methods: A total of 639 women have been followed during pregnancy with repeated measurements of CRP levels (observations: n=2333). ACE intron 16 I/D genotype was determined, and its association with CRP was assessed with adjustment for non-independent observations. Results: CRP levels of ACE D allele carriers were significantly higher than those of the ACE II (wild-type) genotype (p=0.0003, p adj =0.04). This relation was allele-dose dependent (p<10 −4 , p adj <0.02). Association between ACE I/D and CRP was significantly restricted to patients presenting with impaired UPC in univariate (p<0.04) and multivariate analyses (p=0.01). Conclusions:The ACE I/D genotype is significantly associated with CRP elevations during pregnancies complicated by disturbed UPC. Whether this effect on CRP is involved in pathogenesis of preeclampsia has to be elucidated.

Inflammation, depression and cardiovascular disease in women: the role of the immune system across critical reproductive events

“…Dysfunction of the RAAS, in particular changes to angiotensin II, during pregnancy is implicated in preeclampsia. 67 Inflammation (as measured by CRP levels) in pregnant women exhibiting altered utero–placental function was associated with an insertion/deletion polymorphism in the angiotensin-converting-enzyme gene responsible for the conversion of angiotensin II from angiotensin I. 67 Lasting changes to endothelial function are also observed in postpartum women with a past history of preeclampsia who display enhanced vasoconstriction sensitivity to angiotensin II, 68 suggesting that increased sensitivity to angiotensin II may contribute to persisting vasculature dysfunction and increase risk for future CVD.…”

Genetic markers for prediction of early and late onset preeclampsia in pregnant women with preexisting type 1 diabetes mellitus

“…Считается, что D аллель ассо-циируется с повышенной концентрацией ангиотензинпре-вращающего фермента [7,22] и С-реактивного белка [26] в сыворотке крови, сниженной активностью ренина плазмы [6] и компонентов системы антиоксидантной защиты [40], нарушениями процессов вазодилатации [6], а также гисто-патологическими изменениями сосудов матки [11] -то есть с факторами, которые могут быть задействованы в патоге-незе преэклампсии. Все это и обусловливает повышенную склонность к развитию гипертензивных осложнений во время беременности у носителей D аллеля гена АСЕ.…”

Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis

“…Valdez et al (2007) found that the D allele of ACE gene I/D polymorphism was significantly associated with premature rupture of membranes in the Mexican population [17]. Häupl et al (2015) showed a significant association between ACE gene I/D polymorphism and uteroplacental dysfunction in the Middle Eastern Asian population [18]. Uma et al (2008) observed that the DD genotype of ACE gene I/D polymorphism was associated with the development of PTB in the Caucasian population [19].…”