PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

Abstract

The PCMT1 gene encodes the protein repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase, which is known to protect certain neural cells against Bax-induced apoptosis. Previous studies have produced inconsistent results regarding the effects of PCMT1 (rs4816 and rs4552) polymorphisms on neural tube defects (NTDs). Reduced maternal plasma folate levels and/or elevated homocysteine (Hcy) levels are considered to be risk factors for NTDs. In order to clarify the key factors contributing to the apparent discrepancy and investigate gene-environment interaction, we conducted a case-control study including 121 cases and 146 matched controls to investigate the association between the two PCMT1 polymorphisms in fetuses and the risk of NTDs in the Chinese population of Lvliang, which has low folate intake. Maternal plasma folate and Hcy levels were also measured, and the interaction between fetal PCMT1 gene status and maternal folate metabolites was assessed. Maternal plasma folate concentrations in the NTD group were lower than in controls (10.23 vs. 13.08 nmol/L, adjusted P = 0.059), and Hcy concentrations were significantly higher (14.46 vs. 11.65 lmol/L, adjusted P = 0.026). Fetuses carrying the rs4816 AG ? GG genotype, combined with higher maternal plasma Hcy, had a 6.46-fold (95 % CI 1.15-36.46) increased risk of anencephaly. The results of this study imply that the fetal PCMT1 rs4816 polymorphism may play only a weak role in NTD formation and that gene-environment interactions might be more significant.

Maternal biomarkers for early prediction of the neural tube defects pregnancies

“…Five hundred and ninety‐six studies were retrieved by electronic database search. Out of which 33 studies were assessed the level of homocysteine in NTD mothers (Figure 1) (Afman, Blom, Van der Put, & Van Straaten, 2003; Arbour et al, 2002; Aydin et al, 2016; Cadenas‐Benitez et al, 2014; Candito et al, 2008; Ceyhan et al, 2010; Christensen et al, 1999; Deb et al, 2018; Félix, Leistner, & Giugliani, 2004; Gaber, Farag, Soliman, El‐Bassyouni, & El‐Kamah, 2007; Godbole et al, 2011; Groenen et al, 2004; Gu, Li, Cui, & Luo, 2012; Guo et al, 2013; Gupta et al, 2018; Lacasaña et al, 2012; Lucock, Daskalakis, Lumb, Schorah, & Levene, 1998; Martín et al, 2004; Mills et al, 1995; Mobasheri, Keshtkar, & Golalipour, 2010; Paul, Sadhukhan, Munian, Bankura, & Das, 2018; Peker et al, 2016; Ratan et al, 2008; Shaw et al, 2009; Steegers‐Theunissen et al, 1994, 1995; Ubbink et al, 1999; Wang et al, 2008, 2010, 2013; Yildiz et al, 2016; Zhang et al, 2008; Zhao et al, 2006). Arbour et al (2002) reported two different populations (Cree and non‐Cree) we treated them as separate studies so finally for homocysteine we have 34 studies (2,109 cases and 3,514 controls).…”

“…Five hundred and ninety-six studies were retrieved by electronic database search. Out of which 33 studies were assessed the level of homocysteine in NTD mothers ( Lacasaña et al, 2012;Lucock, Daskalakis, Lumb, Schorah, & Levene, 1998;Martín et al, 2004;Mills et al, 1995;Mobasheri, Keshtkar, & Golalipour, 2010;Paul, Sadhukhan, Munian, Bankura, & Das, 2018;Peker et al, 2016;Ratan et al, 2008;Shaw et al, 2009;Steegers-Theunissen et al, 1994Ubbink et al, 1999;Wang et al, 2008Wang et al, , 2010Wang et al, , 2013Yildiz et al, 2016;Zhang et al, 2008;Zhao et al, 2006). Arbour et al (2002) reported two different populations (Cree and non-Cree) we treated them as separate studies so finally for homocysteine we have 34 studies (2,109 cases and 3,514 controls).…”

Different Epigenetic Alterations Are Associated with Abnormal IGF2/Igf2 Upregulation in Neural Tube Defects

“…Recent studies have identified many epigenetic alterations in human or animal fetuses affected with NTDs, including H3K79me2, LINE-1 associated DNA methylation and microRNAs [10] , [14] , [15] , [29] , [30] , demonstrating that multiple epigenetic regulations are involved in the etiology of NTDs. In the present study, the enhanced H3K4ac and depressed H3K27me3 are associated with elevated Igf2 expression in RA-induced NTD mice.…”

Finding the genetic mechanisms of folate deficiency and neural tube defects—Leaving no stone unturned

“…Aberration of protein MTases have been found in diverse cancer types. Previous studies suggested SNPs of PCMT1 , encoding a Bax‐induced apoptosis regulator L‐isoaspartate (D‐aspartate) O‐methyltransferase 1, associated with increased risk for SB, and that the risk was further augmented by high level of maternal plasma Hcy (Wang et al, ; Zhao et al, ; Zhu et al, ). No association for ICMT , MGMT , PRMT1 , and PRMT2 with SB risk was observed (Franke et al, ).…”