Association of growth/differentiation factor 1 gene polymorphisms with the risk of congenital heart disease in the Chinese Han population.

There is evidence suggesting that genetic variants of Nodal signaling may be associated with risk of congenital heart diseases (CHDs), in which several polymorphisms, such as Nodal rs1904589, have been considered to be implicated in the accumulation of the genetic burden of CHD risk with interacting genes. We hypothesized that genetic variants of GDF1, a protein that heterodimerizes with Nodal, may be related to increased CHD susceptibility. In this study, four tagSNPs of GDF1 were genotyped in 310 non-syndromic CHD patients and 320 healthy controls by using PCR-based DHPLC and RFLP. The results showed no statistically significant differences in genotype and allele frequencies between CHDs and controls with any of the analyzed variants of GDF1. However, a weak statistical association existed between GDF1 rs4808870 and conotruncal defects (CTDs) (uncorrected P = 0.027). Further stratified analysis for subtype revealed the SNP AA genotype and A allele have statistical significance in pulmonary atresia (PA) (corrected P = 1.01 × 10(-3) and 0.015, respectively), especially in pulmonary atresia with intact ventricular septum (PA + IVS) (corrected P = 1.67 × 10(-3) and 0.034, respectively). Furthermore, two haplotypes, TGGT and CAGT, were found to be significantly associated with increased CHD susceptibility (corrected P = 3.20 × 10(-3) and 2.73 × 10(-7), respectively). In summary, our results provide evidence that genetic variations of the Nodal-like factor, GDF1 may be associated with CHD risk, and these variations contribute at least in part to the development of some subtypes of CTD in the Chinese Han population.