Sri Sathya Sai Sanjeevani Research Foundation, NH-2, Delhi-Mathura Highway, Baghola, Haryana, District Palwal, Pin- 121102, India.
Present address Sri Sathya Sai Sanjeevani Research Foundation, Kharghar, Navi Mumbai- 410210, Maharashtra, India.
BMC Pediatr. 2023 Jun 15;23(1):290. doi: 10.1186/s12887-023-04095-x.
Congenital 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.
A 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.
Fifty 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.
Caucasian 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.
先天性心脏病（CHD）占所有先天性出生缺陷的三分之一。尽管在全球范围内进行了广泛的研究，但 CHD 的病因仍然难以捉摸。这种发育障碍的表型异质性反复强调了围孕期因素作为风险因素的基因-环境相互作用，以及对散发性和家族性 CHD 的遗传分析表明其具有多基因基础。已经观察到新发和遗传变异的显著相关性。大约有 1/5 的 CHD 在种族独特的印度人群中得到记录，但遗传方面的见解非常有限。这项基于病例对照的关联研究旨在调查印度北部队列中高加索人 SNP 的状况。
从哈里亚纳邦帕尔瓦尔的一家专门的儿科心脏中心招募了 306 例 CHD 病例，分为 n=198 例非发绀型和 n=108 例发绀型。使用 Agena MassARRAY 技术对主要从高加索人全基因组关联研究（GWAS）中优先选择的 23 个 SNP 进行基因分型，并对足够数量的对照进行关联测试。
研究的 50%的 SNP 在等位基因、基因型或亚表型类别中具有实质性关联，验证了它们与疾病表现的强烈相关性。值得注意的是，在 Chr3 上的 CRELD1 中的 rs73118372 观察到最强的等位基因关联（p<0.0001），在 Chr14 上的 MYH6 中的 rs28711516（p=0.00083）和 MYH7 中的 rs735712（p=0.0009）也观察到最强的等位基因关联，并且与非发绀和发绀类别也分别显著相关。rs28711516（p=0.003）和 rs735712（p=0.002）也显示出基因型关联。在 VSD 中观察到最强的关联是 rs735712（p=0.003），而 ASD 亚表型观察到最大的关联。
在印度北部人群中部分复制了高加索人的发现。这些发现表明遗传、环境和社会人口因素的贡献，需要在该研究人群中继续进行调查。
