Abstract:
Background: Congenital heart diseases (CHD) represent the most common birth defect in paediatric population. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. There is still a large proportion of cardiac malformations with unknown precise origin. There is insufficient data in Africa, particularly in Tanzania on the profile of gene expression implicated to cause CHD.
Objective: To determine the gene expression profiles associated with CHD among children aged 0 – 59 months at Muhimbili National Hospital and Jakaya Kikwete Cardiac Institute in Dar es Salaam, Tanzania.
Methodology: A cross-sectional hospital based study was carried out at the Paediatric units at Muhimbili National Hospital (MNH) and Jakaya Kikwete Cardiac Institute (JKCI), which are part of the tertiary hospital in Dar es Salaam, Tanzania. Ethical clearance and permission to conduct the study was sought from MUHAS ethical committee, JKCI and MNH administration respectively. Written informed consents were administered prior to any study procedures. A structured questionnaire was used and blood sample were collected for Real-time reverse transcription Polymerase Chain Reaction (RT-PCR) and baseline routine investigations. Echocardiogram was done to confirm the presence and type of CHD. RT-PCR was performed on a Light Cycler 480 Real Time PCR system (Roche) using standard RT-PCR conditions. Results were analyzed using the Light Cycler 480 Software v1.5. Primer sequences used for RT PCR
Results: A total of 220 children were enrolled into the study, highest percentage (58%) 1 month – 2 year. RT-PCR was performed on 163 samples. NKX2-5 and GATA4 were found to be expressed low in most of the subtypes of CHD. GATA4 and HAND1 were lowly expressed most in septal defects (GATA4 in 34% of Ventricular Septal Defects (VSD) and 27% of Atrial Septal Defects (ASD), while HAND1 in 31% of VSD and 22% of ASD). In conotruncal defects, NKX2-5, TBX5, GATA4 and GATA6 were lowly expressed, with the highest being in TBX5 (29% in Tetralogy of Fallot and 27% in Truncus Arteriosus).
Conclusion and Recommendation: Expression of NKX2-5, TBX5, GATA4, HAND1 and GATA6 may signify a role in development of CHD. Further studies are recommended on protein sequencing of the genes that were lowly expressed in this study so as to know the exact mutations.
