Genetic Analysis of Variants of the MYH6 Gene Promoter in Congenital Atrial Septal Defects

Background: Atrial septal defect (ASD) is one of the common congenital heart diseases. The MYH6 gene has a critical role in cardiac development but the role of MYH6 promoter variants in patients with ASD has not been explored. Methods: In 613 subjects including 320 ASD patients, we investigated the MYH6 gene promoter var-iants and verified the effect on gene expression by using cellular functional experiments and bioinformatics ana-lysis. Results: Eleven variants were identified in the MYH6 gene promoter, of which four variants were found only in ASD patients, and two variants (g.3434G>C and g.4524C>T) were identified for the first time. Cellular func-tional experiments indicated that all four variants reduced the transcriptional activity of the MYH6 gene promoter (p < 0.05). Subsequent analysis through the JASPAR (A database of transcription factor binding profiles) suggests that these variants may alter transcription factor binding sites, which may in turn lead to changes in myocardin subunit expression and ASD formation. Conclusions: Our study for the first time focuses on variants in the pro-moter region of the MYH6 gene in Chinese patients with ASD and the discovered variants have functional sig-nificance. The study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of ASD formation and facilitates clinical diagnosis.