Association between PTCH1 polymorphisms and risk of neural tube defects in a Chinese population. Issue 6 (13th June 2013) - Wang, Zhen
Abstract BACKGROUND SHH signaling pathway plays an important role in the formation of the neural plate and is involved in the regulation of the dorsoventral (DV) axis of the neural tube. Some neural tube defects (NTDs) may be caused through overactivation of the SHH signaling pathway. The PTCH1 gene, encoding a negative regulator of SHH signaling, affects neural tube closure in animal models. However, in humans, the relationship between single nucleotide polymorphisms (SNPs) of the PTCH1 gene and neural tube defects remains unclear. METHODS MassARRAY®GENOTYPER™ was used to genotype 18 SNPs of the PTCH1 gene in 187 NTDs and 212 control samples, to determine whether PTCH1 polymorphisms are related to NTDs. MassARRAY®EpiTYPER™ was performed to assess whether methylation modifications may be associated with SNP genotypes in this Chinese population. RESULT Increased risk for spina bifida was observed with the G allele of c.3944C>T and the T allele of c.1729™2350G>A in female patients when compared to the normal control group. High methylation levels were detected in those controls bearing the G allele of c.3944C>T. Conclusion In summary, polymorphisms of the PTCH1 gene may be genetic predisposing factors for spina bifida in the population studied. In addition, methylation modifications associated with the c.3944C>T polymorphism, may provide protection. Birth Defects Research (Part A) 97:409–415, 2013. © 2013 Wiley Periodicals, Inc.