FLT4 基因多态性影响中国西南地区孤立性室间隔缺损易感性。

FLT4 gene polymorphisms influence isolated ventricular septal defect predisposition in a Southwest China population.

机构信息

The Department of Ultrasound Imaging, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, Yunnan, China.

The Department of Ultrasound Imaging, Fuwai Yunnan Cardiovascular Hospital, Chinese Academy of Medical Sciences, 528 Shahe Road, Kunming, Yunnan, 650032, China.

出版信息

BMC Med Genomics. 2024 Aug 6;17(1):197. doi: 10.1186/s12920-024-01971-y.

DOI:10.1186/s12920-024-01971-y

PMID:39107825

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11302092/

Abstract

BACKGROUND

Ventricular septal defect (VSD) is the most common congenital heart disease. Although a small number of genes associated with VSD have been found, the genetic factors of VSD remain unclear. In this study, we evaluated the association of 10 candidate single nucleotide polymorphisms (SNPs) with isolated VSD in a population from Southwest China.

METHODS

Based on the results of 34 congenital heart disease whole-exome sequencing and 1000 Genomes databases, 10 candidate SNPs were selected. A total of 618 samples were collected from the population of Southwest China, including 285 VSD samples and 333 normal samples. Ten SNPs in the case group and the control group were identified by SNaPshot genotyping. The chi-square (χ) test was used to evaluate the relationship between VSD and each candidate SNP. The SNPs that had significant P value in the initial stage were further analysed using linkage disequilibrium, and haplotypes were assessed in 34 congenital heart disease whole-exome sequencing samples using Haploview software. The bins of SNPs that were in very strong linkage disequilibrium were further used to predict haplotypes by Arlequin software. ViennaRNA v2.5.1 predicted the haplotype mRNA secondary structure. We evaluated the correlation between mRNA secondary structure changes and ventricular septal defects.

RESULTS

The χ results showed that the allele frequency of FLT4 rs383985 (P = 0.040) was different between the control group and the case group (P < 0.05). FLT4 rs3736061 (r = 1), rs3736062 (r = 0.84), rs3736063 (r = 0.84) and FLT4 rs383985 were in high linkage disequilibrium (r > 0.8). Among them, rs3736061 and rs3736062 SNPs in the FLT4 gene led to synonymous variations of amino acids, but predicting the secondary structure of mRNA might change the secondary structure of mRNA and reduce the free energy.

CONCLUSIONS

These findings suggest a possible molecular pathogenesis associated with isolated VSD, which warrants investigation in future studies.

摘要

背景

室间隔缺损（VSD）是最常见的先天性心脏病。虽然已经发现了一些与 VSD 相关的少数基因，但 VSD 的遗传因素仍不清楚。在这项研究中，我们评估了来自中国西南部人群的 10 个候选单核苷酸多态性（SNP）与单纯 VSD 的关联。

方法

基于 34 例先天性心脏病全外显子组测序和 1000 基因组数据库的结果，选择了 10 个候选 SNP。从中国西南部人群中收集了 618 个样本，包括 285 个 VSD 样本和 333 个正常样本。通过 SNaPshot 基因分型鉴定了病例组和对照组中的 10 个 SNP。采用卡方（χ）检验评估 VSD 与每个候选 SNP 的关系。在初始阶段具有显著 P 值的 SNP 进一步通过连锁不平衡进行分析，并使用 Haploview 软件在 34 例先天性心脏病全外显子组测序样本中评估单体型。非常强连锁不平衡的 SNP 箱进一步使用 Arlequin 软件预测单体型。ViennaRNA v2.5.1 预测单体型 mRNA 二级结构。我们评估了 mRNA 二级结构变化与室间隔缺损之间的相关性。

结果

χ 结果显示，FLT4 rs383985 等位基因频率（P=0.040）在对照组和病例组之间存在差异（P<0.05）。FLT4 rs3736061（r=1）、rs3736062（r=0.84）、rs3736063（r=0.84）和 rs383985 高度连锁不平衡（r>0.8）。其中，FLT4 基因中的 rs3736061 和 rs3736062 SNP 导致氨基酸同义变异，但预测 mRNA 的二级结构可能改变 mRNA 的二级结构并降低自由能。