c.620C>T mutation in GATA4 is associated with congenital heart disease in South India.
BACKGROUND
Congenital heart diseases (CHDs) usually refer to abnormalities in the structure and/or function of the heart that arise before birth. GATA4 plays an important role in embryonic heart development, hence the aim of this study was to find the association of GATA4 mutations with CHD among the south Indian CHD patients.


METHODS
GATA4 gene was sequenced in 100 CHD patients (ASD, VSD, TOF and SV) and 200 controls. Functional significance of the observed GATA4 mutations was analyzed using PolyPhen, SIFT, PMut, Plink, Haploview, ESE finder 3.0 and CONSITE.


RESULTS
We observed a total of 19 mutations, of which, one was in 5' UTR, 10 in intronic regions, 3 in coding regions and 5 in 3' UTR. Of the above mutations, one was associated with Atrial Septal Defect (ASD), two were found to be associated with Tetralogy of Fallot (TOF) and three (rs804280, rs4841587 and rs4841588) were strongly associated with Ventricular Septal Defect (VSD). Interestingly, one promoter mutation (-490 to 100 bp) i.e., 620 C>T (rs61277615, p-value = 0.008514), one splice junction mutation (G>A rs73203482; p-value = 9.6e-3, OR = 6.508) and one intronic mutation rs4841587 (p-value = 4.6e-3, OR = 4.758) were the most significant findings of this study. In silico analysis also proves that some of the mutations reported above are pathogenic.


CONCLUSIONS
The present study found that GATA4 genetic variations are associated with ASD, TOF and VSD in South Indian patients. In silico analysis provides further evidence that some of the observed mutations are pathogenic.
Division of Pharmacology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India. mattapallysaidulu@gmail.com.
Saidulu
S
Mattapally
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India. snizam@ccmb.res.in.
Sheikh
S
Nizamuddin
Innova Children's Heart Hospital, Tarnaka, Hyderabad, 500017, India. konasmurthy@gmail.com.
Kona Samba
KS
Murthy
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India. thangs@ccmb.res.in.
Kumarasamy
K
Thangaraj
Division of Pharmacology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India. skbanerjee@thsti.res.in.|Current Address: Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Gurgaon, HR-122016, Haryana, India. skbanerjee@thsti.res.in.
Sanjay K
SK
Banerjee
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D005260:Female; D050991:GATA4 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D005787:Gene Frequency; D023281:Genomics; D006239:Haplotypes; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D055815:Young Adult
D020413:3' Untranslated Regions; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D035683:MicroRNAs