Transforming Growth Factor-Beta1 Gene Polymorphisms in Korean Patients with Pre-eclampsia Shin Young Kim 1 , Ji Hyae Lim 1 , So Yeon Park 1 , Jae Hyug Yang 2 , Moon Young Kim 2 , Min Hyoung Kim 2 , Hyun Mee Ryu 2 1 Laboratory of Medical Genetics, Cheil General Hospital and Women’s Healthcare Center, Seoul, Korea; 2 Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, Korea Introduction Pre-eclampsia (PE) is a severe complication of preg- nancy and, with a worldwide incidence of 2–10%, is one of the leading causes of maternal and perinatal morbidity and mortality. It is associated with insuffi- cient trophoblast invasion of maternal spiral arteries, impaired placental perfusion, and widespread endo- thelial cell dysfunction. 1–3 The events leading to these alterations remain unclear, but emerging evi- dence suggests that an excessive maternal systemic inflammatory response to pregnancy with cytokine- mediated endothelial damage plays a crucial role in the pathogenesis of PE. Transforming growth factor-beta1 (TGF-b1) is a multifunctional cytokine that is produced mainly in Keywords Genetic polymorphism, intrauterine growth restriction, pre-eclampsia, transforming growth factor beta-1 Correspondence Hyun-Mee Ryu, MD, PhD, Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, 1-19 Mukjeong-dong, Jung-gu, Seoul 100-380, Korea. E-mail: hmryu@yahoo.com Submitted July 21, 2009; accepted November 11, 2009. Citation Kim SY, Lim JH, Park SY, Yang JH, Kim MY, Kim MH, Ryu HM. Transforming growth factor- beta1 (TGF-b1) gene polymorphisms in Korean patients with pre-eclampsia. Am J Reprod Immunol 2010; 63: 291–298 doi:10.1111/j.1600-0897.2009.00795.x Problem The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor-beta1 (TGF-b1) gene are associated with development of pre-eclampsia (PE) in Korean women. Method of study We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing. Results The frequencies of the 869CC and combined TC ⁄ CC genotypes were higher in patients with PE than in healthy controls. In the PE with intra- uterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR-complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC ⁄ CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC ⁄ CC genotypes were significantly associated with an increased risk of IUGR-complicated PE compared with the 869TT geno- type. The TGF-b1 c.915G>C polymorphism was not detected in our population. Conclusion Our findings indicate that the TGF-b1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR-complicated PE. ORIGINAL ARTICLE American Journal of Reproductive Immunology 63 (2010) 291–298 ª 2010 John Wiley & Sons A/S 291