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.
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.
Authors: Sung-Eun Kim; Yunping Lei; Sun-Hee Hwang; Bogdan J Wlodarczyk; Saikat Mukhopadhyay; Gary M Shaw; M Elizabeth Ross; Richard H Finnell Journal: Hum Mol Genet Date: 2019-01-15 Impact factor: 6.150
Authors: Siti W Mohd-Zin; Ahmed I Marwan; Mohamad K Abou Chaar; Azlina Ahmad-Annuar; Noraishah M Abdul-Aziz Journal: Scientifica (Cairo) Date: 2017-02-13