Case–control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India

BMC Pediatrics

Research

Radha O Joshi¹  Prabhatha Rashmi Murthy²  Yogesh Sathe³  Subramanian Chellappan³  Krishna Manohar³  Prachi Kukshal⁴  Ajay Kumar⁴  Shadab Ahamad⁴  Soma Guhathakurta⁴ 

[1] Present address Sri Sathya Sai Sanjeevani Research Foundation, Kharghar, Navi Mumbai- 410210, Maharashtra, India;Sri Sathya Sai Sanjeevani Centre for Child Heart Care and Training in Paediatric Cardiac Skills, Navi Mumbai Maharashtra, India;Sri Sathya Sai Sanjeevani International Centre for Child Heart Care & Research, NH-2, Delhi-Mathura Highway, Baghola, Pin 121102, Haryana, District Palwal, India;Sri Sathya Sai Sanjeevani Research Foundation, NH-2, Delhi-Mathura Highway, Baghola, Pin- 121102, Haryana, District Palwal, India;

关键词: Congenital Heart Disease;    North India;    GWAS variants;    Case–control association;   

DOI  :  10.1186/s12887-023-04095-x

 received in 2022-12-01, accepted in 2023-05-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCongenital Heart diseases (CHDs) account for 1/3rd of all congenital birth defects. Etiopathogenesis of CHDs remain elusive despite extensive investigations globally. Phenotypic heterogeneity witnessed in this developmental disorder reiterate gene-environment interactions with periconceptional factors as risk conferring; and genetic analysis of both sporadic and familial forms of CHD suggest its multigenic basis. Significant association of de novo and inherited variants have been observed. Approximately 1/5th of CHDs are documented in the ethnically distinct Indian population but genetic insights have been very limited. This pilot case–control based association study was undertaken to investigate the status of Caucasian SNPs in a north Indian cohort.MethodA total of 306 CHD cases sub-classified into n = 198 acyanotic and n = 108 cyanotic types were recruited from a dedicated tertiary paediatric cardiac centre in Palwal, Haryana. 23 SNPs primarily prioritized from Genome-wide association studies (GWAS) on Caucasians were genotyped using Agena MassARRAY Technology and test of association was performed with adequately numbered controls.ResultsFifty percent of the studied SNPs were substantially associated in either allelic, genotypic or sub-phenotype categories validating their strong correlation with disease manifestation. Of note, strongest allelic association was observed for rs73118372 in CRELD1 (p < 0.0001) on Chr3, rs28711516 in MYH6 (p = 0.00083) and rs735712 in MYH7 (p = 0.0009) both on Chr 14 and were also significantly associated with acyanotic, and cyanotic categories separately. rs28711516 (p = 0.003) and rs735712 (p = 0.002) also showed genotypic association. Strongest association was observed with rs735712(p = 0.003) in VSD and maximum association was observed for ASD sub-phenotypes.ConclusionsCaucasian findings were partly replicated in the north Indian population. The findings suggest the contribution of genetic, environmental and sociodemographic factors, warranting continued investigations in this study population.

【 授权许可】

CC BY   
© The Author(s) 2023

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