Analysis of non-genetic risk factors and FokI polymorphism of Vitamin D Receptor Gene in etiology of preeclampsia cases presented at CMH, Muzaffarabad

Abstract

Preeclampsia (PE) is a pregnancy specific disorder that results in a maternal and perinatal morbidity as well as mortality. Pregnant women with PE are characterized by endothelial cell dysfunction with many sign and symptoms including maternal organs dysfunction, hypertension, proteinuria and fetal growth restrictions. The etiology of PE still remains unknown therefore, screening tools and preventive measures for PE are lacking. Its treatment involves the management of adverse symptoms in PE patients and early delivery which are the only ultimate cure. Assessments of genetic as well as non-genetic risk factors are considered important for early diagnosis of disease that allows close surveillance and preventive approaches. For this case-control study, data on demographic characteristics, reproductive factors, medical factors, anthropometric and lifestyle factors was collected from pregnant women presented at CMH hospital Muzaffarabad between April to July 2021. A total of 300 pregnant females, 60 cases and 240 age matched controls were recruited in this study. Demographic characters and PE risk factors were analyzed by cox regression model, while means of the clinical characters of PE patients and controls were compared by independent sample t-test. For molecular analysis, DNA was extracted from blood samples that are collected from PE patients and controls with their consent. The polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) method was executed to check the maternal FokI rs2228570 polymorphism (T>C) in selected exon 2 of vitamin D receptor (VDR) gene. The aim of current study was to investigate the genetic as well as non-genetic risk factors in preeclampsia affected Kashmiri pregnant women. Results of cox regression model suggested that risk of PE increases significantly (p<0.05) with a family history of hypertension and previous miscarriage history (O.R>1, 95%Cl), while multiparity and proper supplements intake during pregnancy were found to be responsible for decreasing the risk of PE (O.R<1, 95%CI). Clinical characteristics i.e. systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine, serum bilirubin, serum urea, alkaline phosphatase (ALP), alanine transaminase (ALT) and urinary protein were significantly elevated (p<0.0001) in cases compared to controls, while significantly higher (p<0.05) blood haemoglobin (Hb) and platelets count (mean value falls in a normal range) were observed in controls as compared to PE patients. RFLP results of selected exon of VDR gene revealed that 20% PE patients were with homozygous CC genotype and 15% with TC genotype while no controls were found with CC or TC of preeclampsia cases presented at CMH, Muzaffarabad. genotypes which indicate that no disease linked variant was present in controls. These results suggest that there is a link between FokI rs2228570 polymorphism (T>C) of VDR gene and PE risk in our study cohort. In conclusion some factors such as a family history of hypertension and previous miscarriage history were significantly associated with increased PE risk, while multiparity and proper supplements intake during pregnancy were significantly associated with decreased PE risk. Clinical characteristics such as SBP, DBP, ALP, ALT and urinary proteins were found significantly elevated while blood Hb were significantly lower in PE patients. We identified VDR FokI rs2228570 polymorphism in PE patients that suggested the involvement of VDR gene in PE pathology in our population. However, future studies with large sample size should be done to further affirm involvement of FokI polymorphism of VDR gene in PE etiology.