Glutamate carboxypeptidase II gene polymorphisms and neural tube defects in a high-risk Chinese population

Glutamate carboxypeptidase II (GCPII) catalyzes the hydrolysis of N-acetylaspartylglutamate into N-acetylaspartate and glutamate in the brain. Animal experiments suggested that GCPII plays an essential role in early embryonic development. Previous studies provided conflicting results on the effect of the GCPII rs61886492 C>T (or 1561C>T) polymorphism on NTDs. In the Lvliang area of Shanxi province, where the incidence of NTDs is the highest in China, a case–control study was conducted to investigate possible association between the GCPII rs61886492 and rs202676 polymorphisms and NTD risk. Results indicated all the case and control samples displayed the rs61886492 GG genotype. Although no significant differences in rs202676 genotype or allele frequencies were found between the NTD and control groups, the combined AG+GG genotype group was significantly associated with anencephaly (p = 0.03, OR = 2.11, 95% CI, 1.11–4.01), but not with spina bifida or encephalocele. Overall, the rs202676 A>G polymorphism is a potential risk factor for anencephaly. The results of this study suggest that phenotypic heterogeneity may exist among NTDs in this Chinese population.