Genetic Polymorphisms in DNA Repair Gene APE1/Ref-1 and the Risk of Neural Tube Defects in a High-Risk Area of China

Apurinic/apyrimidinic endonuclease 1/redox-factor 1 ( APE1/Ref-1 ) gene encodes a multifunctional protein involved in the DNA base excision repair (BER) pathway, which initiates repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone. APE1/Ref-1 polymorphisms are related to the occurrence of neural tube defects (NTDs), but the association between APE1/Ref-1 polymorphisms and NTDs is not reported in Chinese Han population. The aim of the present study was to evaluate the association of APE1/Ref-1 polymorphism and the risk of NTD occurrence for Han population in a high-risk area of China. APE1/Ref-1 genotypes were determined by iPLEX Gold SNP genotyping. AP sites and folate level of brain tissues were measured. The results showed that three polymorphisms (rs3136817, rs77794916, and rs1760944) of APE1/Ref-1 were statistically associated with NTD subtypes. Allele C of rs3136817, allele T of rs77794916, and allele G of rs1760944 were associated with an increased risk for encephalocele ( OR = 2.52, 95% CI [1.25–5.07], P < 0.01; OR = 1.80, 95% CI [1.04–3.12], P = 0.04; and OR = 1.96, 95% CI [1.12–3.45], P = 0.02), compared with those harboring the alleles T, C, and T, respectively. The folate level in NTDs was lower than that in controls. DNA AP sites in the encephalocele were significantly higher than the control ( P < 0.01). The three polymorphisms of APE1/Ref-1 were significantly related to NTD occurrence, which indicated that APE1/Ref-1 might be a potential genetic risk factor for encephalocele in a high-risk area of NTDs in China.