Characterization of soluble N-ethylmaleimide-sensitive factor attachment protein receptor gene STX18 variations for possible roles in congenital heart diseases

- Many cell types are involved in the mammalian heart development, and any mistakes in the developmentprocess or in the cells may result in congenital heart malformations.
- Syntaxin18 (STX18) plays key roles in transporting vesicle membrane fusion with target compartments of cells and forms complexes with cell cycle-related proteins.
- In this work we found that variant rs12644497 near the 5'UTR and Exon1 of the STX18 gene was associated with the risk of CHD.

Congenital heart disease (CHD) is among the most prevalent and complex congenital anatomic malformations in newborns. Interactions of cardiac progenitor with a broad range of cellular regulatory factors play key roles in the formation of mammalian heart and pathogenesis of CHD. STX18 is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor, which is involved in numeral cellular activities such as organelle assembly and the cell cycle. The aim of this work was to find evidence on whether STX18 variations might be associated with CHD in Chinese Han populations. We evaluated SNPs rs2044, rs33952588, rs61740788, rs12504020 and rs12644497, which are located within the exon or intron sequences of the STX18 gene, for 310 Chinese Han CHD patients and 400 non-CHD controls. Using SPSS software (version 19.0) and the online software OEGE, we conducted statistical analyses and Hardy-Weinberg equilibrium test, respectively. Among the five SNPs identified in the STX18 gene, rs33952588 and rs61740788 had very low genetic heterozygosity. In contrast, the genetic heterozygosity of the remaining three variations rs12504020 and rs12644497 near the 5'UTR and rs2044 within 3'UTR of the STX18 gene was considerably high. Analysis of associations of these genetic variations with the risk of CHD showed that rs12644497 (P value = 0.017 < 0.05) was associated with the risk of CHD, specifically VSD and ASD, whereas rs12504020 (P value = 0.560 > 0.05) and rs2044 (P value = 0.972 > 0.05) were not. The SNP rs12644497 in the STX18 gene was associated with CHD in Chinese Han populations.