Genetic Variations in Angiotensinogen Gene and Risk of Preeclampsia: A Pilot Study

Preeclampsia (PE) is a typical hypertensive disorders of pregnancy (HDP) which can cause substantial morbidity and mortality in both pregnant women and fetuses. The renin-angiotensin system (RAS) genes are the main HDP-causing genes, and Angiotensinogen (AGT) as the initial substrate can directly reflect the activity of the entire RAS. However, the association between AGT SNPs and PE risk has rarely been confirmed. This study was carried out to determine whether AGT SNPs could affect the risk of PE in 228 cases and 358 controls. The genotyping result revealed that the AGT rs7079 TT carrier was related to increased PE risk. Further stratified analysis illustrated that the rs7079 TT genotype significantly increased the PE risk in subgroups of Age < 35, BMI < 25, Albumin (ALB) ≥ 30 and Aspartate aminotransferase (AST) < 30. These findings demonstrated that the rs7079 might be a promising candidate SNP strongly associated with PE susceptibility.

[1]  D. Gill,et al.  Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study , 2022, Hypertension.

[2]  L. Magee,et al.  Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association , 2021, Hypertension.

[3]  S. Boppana,et al.  Association of IL1R1 gene (SNP rs2071374) with the risk of preeclampsia. , 2021, Journal of reproductive immunology.

[4]  Kangdong Liu,et al.  AGT serves as a potential biomarker and drives tumor progression in colorectal carcinoma. , 2021, International immunopharmacology.

[5]  A. Tung,et al.  Long-Term Cardiovascular Disease Risk in Women After Hypertensive Disorders of Pregnancy: Recent Advances in Hypertension , 2021, Hypertension.

[6]  Jun Zhang,et al.  Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China , 2021, JAMA network open.

[7]  Rabia Johnson,et al.  Hypertension in African Populations: Review and Computational Insights , 2021, Genes.

[8]  J. Ambrožič,et al.  Evolution of cardiac geometry and function in women with severe preeclampsia from immediately post-delivery to 1 year postpartum , 2021, The International Journal of Cardiovascular Imaging.

[9]  I. El-Garawani,et al.  Angiotensinogen Gene Missense Polymorphisms (rs699 and rs4762): The Association of End-Stage Renal Failure Risk with Type 2 Diabetes and Hypertension in Egyptians , 2021, Genes.

[10]  Ning Zhang,et al.  Comparative Risks and Predictors of Preeclamptic Pregnancy in the Eastern, Western and Developing World. , 2020, Biochemical pharmacology.

[11]  Yinchuan Xu,et al.  The emerging role of angiotensinogen in cardiovascular diseases , 2020, Journal of cellular physiology.

[12]  N. Perkins,et al.  Preconception Blood Pressure and Its Change Into Early Pregnancy , 2020, Hypertension.

[13]  D. Barrett,et al.  A pilot study of alterations in oxidized angiotensinogen and antioxidants in pre-eclamptic pregnancy , 2020, Scientific Reports.

[14]  A. Dirican,et al.  AGT rs699 and AGTR1 rs5186 gene variants are associated with cardiovascular-related phenotypes in atherosclerotic peripheral arterial obstructive disease , 2019, Irish Journal of Medical Science (1971 -).

[15]  A. Daugherty,et al.  Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis , 2019, Journal of Lipid Research.

[16]  Sergio Lavandero,et al.  Counter-regulatory renin–angiotensin system in cardiovascular disease , 2019, Nature Reviews Cardiology.

[17]  S. Balakrishna,et al.  Novel association of SNP rs479200 in EGLN1 gene with predisposition to preeclampsia. , 2019, Gene.

[18]  Eriko Takimoto-Ohnishi,et al.  Renin–angiotensin system research: from molecules to the whole body , 2019, The Journal of Physiological Sciences.

[19]  N. Sun,et al.  A new model of the mechanism underlying lead poisoning: SNP in miRNA target region influence the AGT expression level , 2019, Hereditas.

[20]  Xiaoqiong Gu,et al.  An Angiotensinogen Gene Polymorphism (rs5050) Is Associated with the Risk of Coronary Artery Aneurysm in Southern Chinese Children with Kawasaki Disease , 2019, Disease markers.

[21]  P. Ostrosky-Wegman,et al.  Angiotensinogen rs5050 germline genetic variant as potential biomarker of poor prognosis in astrocytoma , 2018, PloS one.

[22]  A. Franx,et al.  Recurrence of pre‐eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta‐analysis , 2018, BJOG : an international journal of obstetrics and gynaecology.

[23]  L. Magee,et al.  The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. , 2018, Pregnancy hypertension.

[24]  A. Daugherty,et al.  Renin-Angiotensin System and Cardiovascular Functions , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[25]  S. Karumanchi,et al.  Genetic predisposition to preeclampsia is conferred by fetal DNA variants near FLT1, a gene involved in the regulation of angiogenesis. , 2017, American journal of obstetrics and gynecology.

[26]  S. Karakuş,et al.  Renalase gene polymorphism is associated with increased blood pressure in preeclampsia. , 2016, Pregnancy hypertension.

[27]  B. Altun,et al.  Association between urinary angiotensinogen, hypertension and proteinuria in pregnant women with preeclampsia , 2015, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[28]  A. Shennan,et al.  Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. , 2015, Obstetrics and gynecology.

[29]  Ashok Kumar,et al.  Human angiotensinogen +11525 C/A polymorphism modulates its gene expression through microRNA binding. , 2013, Physiological genomics.

[30]  D. Chou,et al.  Global and regional estimates of preeclampsia and eclampsia: a systematic review. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[31]  Yeong-Hoon Kim,et al.  Angiotensinogen Polymorphisms and Post-Transplantation Diabetes Mellitus in Korean Renal Transplant Subjects , 2013, Kidney and Blood Pressure Research.

[32]  Y. Lei,et al.  Angiotensinogen Gene M235T and T174M Polymorphisms and Susceptibility of Pre‐Eclampsia: A Meta‐Analysis , 2012, Annals of human genetics.

[33]  A. Daugherty,et al.  Molecular and Pathophysiological Features of Angiotensinogen: A Mini Review. , 2011, North American journal of medicine & science.

[34]  L. Jorde,et al.  Genotype–phenotype analysis of angiotensinogen polymorphisms and essential hypertension: the importance of haplotypes , 2010, Journal of hypertension.

[35]  V. Garovic,et al.  Review: Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test? , 2008, Therapeutic advances in cardiovascular disease.

[36]  C. V. van Duijn,et al.  Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease , 2008, Hypertension.

[37]  R. Schmieder,et al.  Renin-angiotensin system and cardiovascular risk , 2007, The Lancet.

[38]  James J. Walker,et al.  Pre-eclampsia , 2000, The Lancet.

[39]  Zehra Jamil,et al.  Polymorphism of the renalase gene in gestational diabetes mellitus , 2016, Endocrine.