Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes

Genes

卷:11

Domenico Lio¹  Letizia Scola¹  RosaMaria Giarratana¹  CarmelaRita Balistreri¹  Tiziana Fragapane²  ClaudiaLeonarda Ammoscato³  Maria Piccione³ 

[1] Clinical Pathology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90100 Palermo, Italy;

[2] Department of Neonatology, University Hospital Galway, h91 Galway, Ireland;

[3] Regional Reference Center for the Control and Treatment of Down Syndrome and Other Chromosomal and Genetic Diseases, Medical Genetics University of Palermo, Villa Sofia/Cervello-United Hospitals, 90100 Palermo, Italy;

关键词: Down syndrome;    heart defects;    SNPs;    IFNR;    VEGFA;   

DOI  :  10.3390/genes11121428

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown