Association Between ISL1 Variants and Susceptibility to Ventricular Septal Defect in a Chinese Cohort

It has previously been reported that ISLET1 (ISL1) plays a fundamental role in cardiac morphogenesis. This study investigated the possible association between variants in the ISL LIM homeobox 1 (ISL1) gene and congenital ventricular septal defect (VSD) in a Chinese cohort. A total of 512 congenital VSD patients and 612 unrelated age- and sex-matched healthy control subjects were enrolled in this study. Genotypes for three variants in ISL1 (rs3762977, IVS1+17C > T, and rs1017) were determined. We found that the rs3762977 and IVS+17C > T variants were closely associated with the risk of developing VSD. Carriers of the GG genotype of rs3762977 and the TT genotype of IVS+17C > T were less likely to have VSD, whereas variants in rs1701 did not affect the VSD risk. The haplotypes (rs3762977)G-(rs1017)A-TIVS+17 and (rs3762977)G-T-rs1017-TIVS+17 represented a protective effect against VSD. None of these ISL1 variants showed any association with VSD type according to defect location and VSD severity according to defect size. These findings suggest that ISL1 genetic polymorphisms are associated with occurrence of VSD, thus they may be useful as molecular markers for prediction of VSD.