Genetic Predisposition for Preeclampsia in a Population of Pregnant Women in Adama and the Surrounding Areas, Ethiopia
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Date
2020-12
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Addis Abeba University
Abstract
Introduction: Preeclampsia (PE) is a global health problem, which is the major cause of
maternal and fetal deaths. The majority of PE related deaths occur in low- and middle-income
countries with limited-resource. Currently there is no cure for the syndrome, delivery remains
the only option. The etiology of PE is not elucidated yet. However, several studies suggest a
hereditary predisposition for acquiring the disease. Accordingly, studies have showed the role
of killer cell immunoglobulin-like receptor’s (KIRs) expressed by uterine natural killer (uNK)
cells and human leukocyte antigen-C (HLA-C) in familial predisposition of PE. In addition,
recent evidences indicated the probable role of the CD99 expression in the pathogenesis of PE
in a fetal sex dependent fashion. Such evidences are lacking in the Ethiopian context.
Therefore, the general aim of the study was to evaluate the genetic predisposition for PE in a
cohort of Ethiopian pregnant women.
Methods: A case-control study design was used. The study was conducted at Adama
Regional Referral Hospital. We involved 288 (131 PE, 157 controls) study participants for the
first part of the study and 241 (105 PE, 136 controls) study participants for the second part of
the study. The demographic and clinical data was collected using questionnaire. The maternal
venous and cord blood was collected, and DNA extracted using QIAGEN reagent. The DNA
was amplified using traditional polymerase chain reaction (PCR) and real time quantitative
PCR (RT qPCR) using TaqMan
TM
Genotyping master mix (Applied Biosystems by Thermo
Fisher Scientific, Waltham, MA, USA) and published primers. The data analysis was done
using SPSS version 26.0. The Chi-Square test was used to evaluate the association between
variables. The p-value <0.05 was used as cut-off point for the association of variables.
Results: the mean age, systolic and diastolic blood pressures were higher while gestation age
was lower in PE group compared to controls. A statistically significant association was
observed in frequency of KIRAA, KIR2DS1 and in a subset of non-self HLA-C between the
PE and control groups. In addition, a statistically significant association was showed in
maternal regulatory region low CD99 expression genotype (CC) between PE mothers of
males compared to controls.
Conclusion: The KIRAA plays role in predisposition of PE while KIR2DS1 may play role in
protection of Ethiopian pregnant women from PE. In addition, maternal regulatory region CC
genotype may predispose mothers for PE in fetal sex-dependent fashion.
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Keywords
Preeclampsia, KIRAA, HLA-C2, male fetus, CD99