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

IF 2.1 4区医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-08-06 DOI:10.1186/s12920-024-01971-y

Yunhan Zhang, Xiaoli Dong, Jun Zhang, Miao Zhao, Jiang Wang, Jiayou Chu, Zhaoqing Yang, Shaohui Ma, Keqin Lin, Hao Sun, Zhiling Luo

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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 (χ²) 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 χ² 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 (r² = 1), rs3736062 (r² = 0.84), rs3736063 (r² = 0.84) and FLT4 rs383985 were in high linkage disequilibrium (r² > 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.

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FLT4基因多态性对中国西南地区孤立性室间隔缺损易感性的影响

背景：室间隔缺损（VSD）是最常见的先天性心脏病：室间隔缺损（VSD）是最常见的先天性心脏病。虽然已经发现了少量与 VSD 相关的基因，但 VSD 的遗传因素仍不清楚。本研究评估了中国西南地区人群中 10 个候选单核苷酸多态性（SNPs）与孤立性 VSD 的相关性：方法：根据 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，筛选出 10 个候选 SNPs。方法：根据 34 个先天性心脏病全外显子组测序结果和 1000 Genomes 数据库，筛选出 10 个候选 SNPs。通过 SNaPshot 基因分型，确定了病例组和对照组中的 10 个 SNPs。采用卡方（χ2）检验来评估 VSD 与每个候选 SNP 之间的关系。使用 Haploview 软件对 34 个先天性心脏病全外显子组测序样本中的单倍型进行评估。通过 Arlequin 软件，进一步利用处于极强连锁不平衡状态的 SNPs bins 预测单倍型。ViennaRNA v2.5.1 预测了单倍型 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：χ2结果显示，FLT4 rs383985的等位基因频率（P = 0.040）在对照组和病例组之间存在差异（P 2 = 1），rs3736062（r2 = 0.84）、rs3736063（r2 = 0.84）和FLT4 rs383985处于高度连锁不平衡状态（r2 > 0.8）。其中，FLT4基因中的rs3736061和rs3736062 SNP导致氨基酸的同义变异，但预测mRNA的二级结构可能会改变mRNA的二级结构，降低自由能：这些发现提示了与孤立性 VSD 相关的可能的分子发病机制，值得在今后的研究中加以探讨。

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来源期刊

BMC Medical Genomics 医学-遗传学

CiteScore

3.90

自引率

0.00%

发文量

243

审稿时长

3.5 months

期刊介绍： BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.