Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes.
Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes.
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唐氏综合征患者心脏缺陷的易感性与ha21干扰素受体簇和VEGFA基因的单核苷酸多态性有关
DOI：
10.3390/genes11121428
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发表时间：
2020-11-28
期刊：
影响因子：
3.5
通讯作者：
Piccione M
中科院分区：
文献类型：
--
作者：
Balistreri CR;Ammoscato CL;Scola L;Fragapane T;Giarratana RM;Lio D;Piccione M
背景：先天性心脏缺陷（CHD）存在于约40-60%的唐氏综合征（DS）新生儿中。患有DS的患者也可以发展为获得性心脏疾病。小鼠模型表明，位于人类21号染色体（HSA 21）上的一个关键的3.7 Mb区域可以解释与CHD的关联。该区域包括编码干扰素受体（IFN-R）的基因簇（IFNAR 1、IFNAR 2、IFNGR 2、IL 10 RB）。位于不同染色体上的其他基因，如血管内皮生长因子A（VEGFA），已被证明与心脏缺陷有关。因此，我们研究了IFNAR 2，IFNGR 2，IL 10 RB和VEGFA基因的单核苷酸多态性（SNP）与DS患者中CHD或获得性心脏缺陷的存在之间的关联。研究方法：使用KASPar分析对DS个体（n = 102）和年龄和性别匹配的对照（n = 96）进行4种SNP（rs 2229207、rs 2834213、rs 2834167和rs3025039）的基因分型。结果如下：我们发现IFNGR 2 rs 2834213 G纯合基因型和IL 10 RB rs 2834167 G阳性基因型在DS患者中更常见，并且与心脏疾病显著相关，而VEGFA rs3025039 T阳性基因型（T/*）在CHD患者中不太常见。结论：我们确定了一些候选的CHD和DS中获得性心脏缺陷的风险SNP。我们的数据表明，一个复杂的架构的风险等位基因的相互作用的影响可能有助于DS表型的高变异性。
Background: Congenital heart defects (CHDs) are present in about 40–60% of newborns with Down syndrome (DS). Patients with DS can also develop acquired cardiac disorders. Mouse models suggest that a critical 3.7 Mb region located on human chromosome 21 (HSA21) could explain the association with CHDs. This region includes a cluster of genes (IFNAR1, IFNAR2, IFNGR2, IL10RB) encoding for interferon receptors (IFN-Rs). Other genes located on different chromosomes, such as the vascular endothelial growth factor A (VEGFA), have been shown to be involved in cardiac defects. So, we investigated the association between single nucleotide polymorphisms (SNPs) in IFNAR2, IFNGR2, IL10RB and VEGFA genes, and the presence of CHDs or acquired cardiac defects in patients with DS. Methods: Individuals (n = 102) with DS, and age- and gender-matched controls (n = 96), were genotyped for four SNPs (rs2229207, rs2834213, rs2834167 and rs3025039) using KASPar assays. Results: We found that the IFNGR2 rs2834213 G homozygous genotype and IL10RB rs2834167G-positive genotypes were more common in patients with DSand significantly associated with heart disorders, while VEGFA rs3025039T-positive genotypes (T/*) were less prevalent in patients with CHDs. Conclusions: We identified some candidate risk SNPs for CHDs and acquired heart defects in DS. Our data suggest that a complex architecture of risk alleles with interplay effects may contribute to the high variability of DS phenotypes.
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DOI：
10.1183/16000617.0098-2016
发表时间：
2017-01
期刊：
European respiratory review : an official journal of the European Respiratory Society
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Ling KH;Hewitt CA;Tan KL;Cheah PS;Vidyadaran S;Lai MI;Lee HC;Simpson K;Hyde L;Pritchard MA;Smyth GK;Thomas T;Scott HS
通讯作者：
Scott HS
影响因子：
9.8
作者：
Ackerman, Christine;Locke, Adam E.;Maslen, Cheryl L.
通讯作者：
Maslen, Cheryl L.
DOI：
10.1006/bbrc.1998.9743
发表时间：
1999-01-19
影响因子：
3.1
作者：
Greber-Platzer, S;Schatzmann-Turhani, D;Lubec, G
通讯作者：
Lubec, G
影响因子：
5
作者：
KHOURY, MJ;ERICKSON, JD
通讯作者：
ERICKSON, JD