c.620C>T mutation in GATA4 is associated with congenital heart disease in South India

BMC Medical Genetics

Sanjay K Banerjee¹  Kumarasamy Thangaraj⁴  Kona Samba Murthy²  Sheikh Nizamuddin⁴  Saidulu Mattapally³ 

[1] Current Address: Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Gurgaon HR-122016, Haryana, India;Innova Children’s Heart Hospital, Tarnaka, Hyderabad 500017, India;Division of Pharmacology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India;CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India

关键词: VSD;    TOF;    ASD;    South Indian patients;    Mutation;    GATA4;    Congenital heart disease;   

Others  :  1171815
DOI  :  10.1186/s12881-015-0152-7

 received in 2014-09-02, accepted in 2015-01-30,  发布年份 2015

【 摘 要 】

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.

Method

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.

Conclusion

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.

【 授权许可】

   
2015 Mattapally et al.; licensee BioMed Central .

【 图 表 】

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