{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:04:03Z","timestamp":1782903843745,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The ACE gene encodes the angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system. Increased ACE activity may cause abnormal regulation of placental circulation and angiogenesis, resulting in adverse pregnancy outcomes. Previous studies have reported that the insertion\/deletion (I\/D) polymorphism of the ACE gene is associated with the development of preterm birth (PTB). However, results of the association between ACE gene I\/D and PTB are inconsistent in various populations. Therefore, we performed a case-control study and a meta-analysis to evaluate the association between ACE I\/D polymorphism and PTB. Materials and Methods: We analyzed a total of 254 subjects (111 patients with PTB and 143 women at \u226538 weeks gestation) for the case-control study. For the meta-analysis, we searched Google Scholar, PubMed, and NCBI databases with the terms \u201cACE,\u201d \u201cangiotensin-converting enzyme,\u201d \u201cpreterm birth,\u201d \u201cpreterm delivery,\u201d and their combinations. Results: Our results of the case-control study indicated that ACE I\/D polymorphism is significantly associated with PTBs in the overdominant genetic model (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.347\u20130.949, p = 0.029) and that the ID genotype of ACE I\/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333\u20130.986, p = 0.043). Similarly, the meta-analysis showed that the OR for the ACE gene ID genotype was 0.66 (95% CI 0.490\u20130.900, p &lt; 0.01). Conclusion: The ACE gene ID genotype has a significant association with PTB and is a protective factor for PTB. A larger sample set and functional studies are required to further elucidate of our findings.<\/jats:p>","DOI":"10.3390\/medicina55060264","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T11:39:47Z","timestamp":1560166787000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I\/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis"],"prefix":"10.3390","volume":"55","author":[{"given":"Noo Ri","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Natural Science, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Wook","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Science, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Science, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Dan","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Dankook University Hospital, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Wan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Dankook University Hospital, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Jun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Science, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1046\/j.1365-3016.2001.00014.x","article-title":"Pregnancy Outcomes and Community Health: The POUCH Study of Preterm Delivery","volume":"15","author":"Holzman","year":"2011","journal-title":"Paediatr. Perrinat. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2471\/BLT.08.062554","article-title":"The Worldwide Incidence of Preterm Birth: A Systematic Review of Maternal Mortality and Morbidity","volume":"88","author":"Beck","year":"2010","journal-title":"Bull. World Health Organ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9966","DOI":"10.1073\/pnas.1705899114","article-title":"Replication and Refinement of a Vaginal Microbial Signature of Preterm Birth in Two Racially Distinct Cohorts of US Women","volume":"114","author":"Callahan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1046\/j.1471-0528.2003.00021.x","article-title":"Classification and Heterogeneity of Preterm Birth","volume":"110","author":"Moutquin","year":"2003","journal-title":"Int. J. Obstet. Gynaecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.bcmd.2004.04.011","article-title":"Thrombophilic Polymorphisms in Preterm Delivery","volume":"33","author":"Valdez","year":"2004","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1011353216619","article-title":"Stress and Preterm Birth: Neuroendocine, Immune\/Inflammatory, and Vascular Mechanisms","volume":"5","author":"Wadhwa","year":"2001","journal-title":"Matern. Child Health J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejogrb.2006.10.005","article-title":"Genetic Polymorphisms in Vasoactive Genes and Preeclampsia: A Meta-Analysis","volume":"131","author":"Medica","year":"2007","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3109\/10641959309079449","article-title":"Expression of Renin and Angiotensinogen Genes in Preeclamptic and Normal Human Placental Tissue","volume":"12","author":"Sowers","year":"1993","journal-title":"Hypertens. Pregnancy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1161\/01.CIR.87.6.1816","article-title":"Molecular Biology of the Renin-Angiotensin System","volume":"87","author":"Griendling","year":"1993","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/1440-1681.12734","article-title":"The Intrauterine Renin-Angiotensin Systerm: Sex-Specific Effects on the Prevalence of Spontaneous Preterm Birth","volume":"44","author":"Pringle","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_11","first-page":"1","article-title":"The Gene Variants of Maternal\/Fetal Renin-Angiotensin System in Preeclampsia: A Hybrid Case-Parent\/Mother-Control Study","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejogrb.2011.04.028","article-title":"Haplotype-Based Association of ACE I\/D, AT1R 1166A>C, and AGT M235T Polymorphisms in Renin-Angiotensin-Aldosterone System Genes in Korean Women with Idiopathic Recurrent Spontaneous Abortions","volume":"158","author":"Choi","year":"2011","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15377","DOI":"10.1016\/S0021-9258(18)98626-6","article-title":"Structure of the Angiotensin I-Converting Enzyme Gene. Two Alternate Promoters Correspond to Evolutionary Steps of a Duplicated Gene","volume":"266","author":"Hubert","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.4238\/2012.May.21.1","article-title":"Meta-Analysis of Angiotensin-Converting Enzyme I\/D Polymorphism as a Risk Factor for Preeclampsia in Chinese Women","volume":"11","author":"Zhong","year":"2012","journal-title":"Genet. Mol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1046\/j.1523-1755.2001.0600031124.x","article-title":"Angiotensin-Converting Enzyme (ACE) I\/D Genotype and Renal ACE Gene Expression","volume":"60","author":"Mizuiri","year":"2001","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1055\/s-0029-1211289","article-title":"The Uteroplacental Renin-Angiotensin System: A Review","volume":"102","author":"Hagemann","year":"1994","journal-title":"Exp. Clin. Endocinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3317\/jraas.2007.026","article-title":"Genetic Polymorphisms of the Renin-Angiotensin System in Preterm Delivery and Premature Rupture of Membranes","volume":"8","author":"Perez","year":"2007","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1177\/1470320314539181","article-title":"Angiotensin Converting Enzyme Intron16 Insertion\/Deletion Genotype is Associated with Plasma C-Reactive Protein Concentration in Uteroplacental Dysfuction","volume":"16","author":"Zimmermann","year":"2015","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ejogrb.2008.07.006","article-title":"Correlation of Angiotensin Converting Enzyme Activity and the Genotypes of the I\/D Polymorphism in the ACE Gene with Preterm Birth and Birth Weight","volume":"141","author":"Uma","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.11648\/j.jgo.20140204.11","article-title":"Lack of Association between ACE I\/D and AGTR1 A1166C Gene Polymorphisms and Preeclampsia in Turkish Pregnant Women of Trakya Region","volume":"2","author":"Alkanli","year":"2014","journal-title":"J. Gynecol. Obstet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1055\/s-2005-872442","article-title":"Insertion\/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Preeclampsia in Japanese Patients","volume":"31","author":"Kobashi","year":"2005","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neulet.2016.02.049","article-title":"Calcium Homeostasis Modulator 1 Gene P86L Polymorphism and the Risk for Alzheimer\u2019s Disease: A Meta-Analysis","volume":"619","author":"Mun","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000356774","article-title":"Perinatal Outcomes of Pregnancies Complicated by Maternal Depression with or Without","volume":"105","author":"Engelstad","year":"2014","journal-title":"Neonatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cccn.2003.11.010","article-title":"The association between preeclampsia and angiotensin-converting enzyme insertion\/deletion polymorphism","volume":"341","author":"Dirican","year":"2004","journal-title":"Clinica Chimica Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/nar\/20.6.1433-a","article-title":"PCR Detection of the Insertion\/Deletion Polymorphism of the Human Angiotensin Converting Enzyme Gene (DCP) (Dipeptidyl Carboxypeptidase 1)","volume":"20","author":"Rigat","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Borenstein, M., Hedges, L.M., Higgins, J.P., and Rothstein, H.R. (2009). Introduction to Meta-Analysis, John Wiley & Sons.","DOI":"10.1002\/9780470743386"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ptr.5524","article-title":"The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials","volume":"30","author":"Karawi","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in Meta-Analysis Detected by a Simple, Graphical Test","volume":"315","author":"Egger","year":"1997","journal-title":"Br. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jclinepi.2007.11.010","article-title":"Contour-Enhanced Mata-Analysis Funnel Plots Help Distinguish Publication Bias from Other Causes of Asummetry","volume":"61","author":"Jaimem","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000237743","article-title":"Relationship between Preterm Labor and Thrombophilic Gene Polymorphism: A Prospective Sequential Cohort Study","volume":"68","author":"Uvuz","year":"2009","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rothstein, H.R., Sutton, A.J., and Borenstein, M. (2005). Publication Bias in Meta-Analysis: Prevention, Assessment and Adjustments, John Wiley and Sons.","DOI":"10.1002\/0470870168"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1177\/1470320312448950","article-title":"Preecalmpsia and Angiotensin Converting Enzyme (ACE) I\/D and Angiotensin II Type-1 Receptor (AT1R) A1166C Polymorphisms: Association with ACE I\/D Polymorphism","volume":"14","author":"Rahimi","year":"2012","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"323","DOI":"10.29252\/ijrm.14.5.323","article-title":"Significant Correlation of Angiotensin Converting Enzyme and Glycoprotein IIIa Genes Polymorphisms with Unexplained Recurrent Pregnancy Loss in North of Iran","volume":"14","author":"Fazelnia","year":"2016","journal-title":"Int. J. Reprod. BioMed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s10815-012-9870-3","article-title":"Angiotensin-Converting Enzyme Insertion\/Deletion (I\/D) Polymorphisms and Recurrent Pregnancy Loss: A Meta-Analysis","volume":"29","author":"Yang","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ijcard.2003.05.017","article-title":"Angtiotensin-Converting Enzyme and P22phox Polymorphisms and the Risk of Coronary Heart Disease in a Low-Risk Spanish Population","volume":"95","year":"2004","journal-title":"Int. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1684\/ejd.2011.1279","article-title":"Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Vitiligo: Protective and Predisposing Effects of Genotypes in Disease Susceptibility and Progression","volume":"21","author":"Tippisetty","year":"2011","journal-title":"Eur. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/1470320309102317","article-title":"Association between the Angiotensin-Converting Enzyme (Insertion\/Deletion) and Angiotensin II Type 1 Receptor (A1166C) Polymorphisms and Breast Cancer Among Brazilian Women","volume":"10","author":"Costa","year":"2009","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0140-6736(05)67531-9","article-title":"What Makes a Good Genetic Association Study?","volume":"366","author":"Hattersley","year":"2005","journal-title":"Lancet"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/6\/264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:57:22Z","timestamp":1760187442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/6\/264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,10]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["medicina55060264"],"URL":"https:\/\/doi.org\/10.3390\/medicina55060264","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,10]]}}}