23. Association polymorphism of gene-related preeclampsia, Fms-related tyrosine kinase 1 (FLT1), with peripartum cardiomyopathy

Abstract

Introduction: Preeclampsia (PE) is one of the most serious hypertension disorder during pregnancy. Several polymorphisms have been correlated with an increased risk of PE, one of them is FLT1 gene. FLT1 gene encodes soluble Fms like tyrosine Kinase 1 (sFlt-1), an anti-angiogenic factor that plays crucial role in PE pathogenesis. PE is often cited as a risk factor for peripartum cardiomyopathy (PPCM). However, until now, no study has evaluated FLT1 polymorphism in relation to PPCM incidence. Aims: To screen whether the Fms-related tyrosine kinase 1 (FLT1) gene polymorphism contributes to genetic susceptibility to peripartum cardiomyopathy (PPCM). Methods: An analytic observational study with a case-control design was conducted at Integrated Cardiac Service Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. The PPCM cases and controls were enrolled. Baseline characteristic data were collected, and blood samples were analyzed for FLT1 gene (rs722503 and rs12584067) polymorphism by PCR amplification followed by restriction fragment length polymorphism (RFLP). Serum levels of sFlt-1 were measured by sandwich ELISA. Results: A total of 134 patients, 67 PPCM cases and 67 control, were included in this study. Genotyping of FLT1 showed T/T (rs722503) and G/G (rs12584067) genotypes were more frequent in PPCM cases with significant differences (p = 0.020 and p = 0.042, respectively). However, FLT1 polymorphism in PPCM with PE groups had higher significant genotype differences for rs12584067 than other groups (p < 0.001). Evidence of PE was found in 45% of PPCM cases. FLT1 polymorphism in PPCM with PE groups had significantly increased serum levels than other groups (p < 0.001). Conclusion: The study shows the possible association of FLT1 polymorphisms with gene expression leading to PPCM related to preeclampsia.