研究与室间隔缺损（VSD）相关的变异凸显了巴基斯坦人群独特的遗传结构。

Study of variants associated with ventricular septal defects (VSDs) highlights the unique genetic structure of the Pakistani population.

机构信息

Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, 54590, Pakistan.

出版信息

Ital J Pediatr. 2022 Jul 23;48(1):124. doi: 10.1186/s13052-022-01323-5.

DOI:10.1186/s13052-022-01323-5

PMID:35870951

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9308904/

Abstract

BACKGROUND

Ventricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the remarkable progress in medication, treatment and surgical procedure for VSDs, the genetic etiology of VSDs is still in infancy because of the complex genetic and environmental interactions.

METHODS

Three hundred fifty subjects (200 VSD children and 150 healthy controls) were recruited from different pediatric cardiac units. Pediatric clinical and demographic data were collected. A total of six variants, rs1017 (ISL1), rs7240256 (NFATc1), rs36208048 (VEGF), variant of HEY2, rs11067075 (TBX5) and rs1801133 (MTHFR) genes were genotyped by tetra-ARMS PCR and PCR-RFLP methods.

RESULTS

The results showed that in cases, the rs1017 (g.16138A > T) variant in the ISL1 gene has an allele frequency of 0.42 and 0.58 respectively for the T and A alleles, and 0.75 and 0.25 respectively in the controls. The frequencies of the AA, TA and TT genotypes were, 52%, 11% and 37% in cases versus 21%, 8% and 71% respectively in the controls. For the NFATc1 variant rs7240256, minor allele frequency (MAF) was 0.43 in cases while 0.23 in controls. For the variant in the VEGF gene, genotype frequencies were 0% (A), 32% (CA) and 68% (CC) in cases and 0.0%, 33% and 67% respectively in controls. The allele frequency of C and A were 0.84 and 0.16 in cases and 0.83 and 0.17 respectively in controls. The TBX5 polymorphism rs11067075 (g.51682G > T) had an allelic frequency of 0.44 and 0.56 respectively for T and G alleles in cases, versus 0.26 and 0.74 in the controls. We did not detect the presence of the HEY2 gene variant (g.126117350A > C) in our pediatric cohort. For the rs1801133 (g.14783C > T) variant in the MTHFR gene, the genotype frequencies were 25% (CC), 62% (CT) and 13% (TT) in cases, versus 88%, 10% and 2% in controls. The ISL1, NFATc1, TBX5 and MTHFR variants were found to be in association with VSD in the Pakistani pediatric cohort whilst the VEGF and HEY2 variants were completely absent in our cohort.

CONCLUSION

We propose that a wider programme of genetic screening of the Pakistani population for genetic markers in heart development genes would be helpful in reducing the risk of VSDs.

摘要

背景

室间隔缺损（VSD）是导致婴儿生命早期心脏畸形的主要死因之一。新生儿 VSD 的患病率高达 4%。尽管在 VSD 的药物治疗、治疗和手术方面取得了显著进展，但由于复杂的遗传和环境相互作用，VSD 的遗传病因仍处于起步阶段。

方法

从不同的儿科心脏单位招募了 350 名受试者（200 名 VSD 儿童和 150 名健康对照）。收集儿科临床和人口统计学数据。总共对六个变体（rs1017（ISL1）、rs7240256（NFATc1）、rs36208048（VEGF）、HEY2 变体、rs11067075（TBX5）和 rs1801133（MTHFR）基因进行了基因分型，采用四等位基因 ARMS-PCR 和 PCR-RFLP 方法。

结果

结果表明，在病例中，ISL1 基因中的 rs1017（g.16138A>G>T）变体的等位基因频率分别为 T 等位基因 0.42 和 A 等位基因 0.58，对照分别为 0.75 和 0.25。AA、TA 和 TT 基因型的频率分别为 52%、11%和 37%在病例中，8%、8%和 71%分别在对照组中。对于 NFATc1 变体 rs7240256，次要等位基因频率（MAF）在病例中为 0.43，在对照中为 0.23。对于 VEGF 基因的变体，基因型频率分别为 0%（A）、32%（CA）和 68%（CC）在病例中，0.0%、33%和 67%分别在对照组中。C 和 A 的等位基因频率分别为 0.84 和 0.16 在病例中，0.83 和 0.17 分别在对照组中。TBX5 多态性 rs11067075（g.51682G>T）在病例中的等位基因频率分别为 T 和 G 等位基因 0.44 和 0.56，对照分别为 0.26 和 0.74。我们在儿科队列中未检测到 HEY2 基因变体（g.126117350A>G）的存在。对于 MTHFR 基因中的 rs1801133（g.14783C>T）变体，病例中的基因型频率分别为 25%（CC）、62%（CT）和 13%（TT），对照分别为 88%、10%和 2%。ISL1、NFATc1、TBX5 和 MTHFR 变体与巴基斯坦儿科队列中的 VSD 相关，而 VEGF 和 HEY2 变体在我们的队列中完全不存在。