C677T mutation in methylenetetrahydrofolate reductase gene and neural tube defects: Should Japanese women undergo gene screening before pregnancy?

Abstract

We analyzed the role of maternal C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene on spina bifida development in newborns. A total of 115 mothers who had given birth to a spina bifida child (SB mothers) gave 10 mL of blood together with written informed consent. The genotype distribution of C677T mutation was assessed and compared with that of the 4517 control individuals. The prevalence of the homozygous genotype (TT) among SB mothers was not significantly different from that among the controls (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.31-1.25; P = 0.182), suggesting that MTHFR 677TT genotype in Japan is not associated with spina bifida development in newborns. The T allele frequency was not increased in SB mothers (34.8%) as compared to that of the control individuals (38.2%). Further, the internationally reported association between the two groups was found to be similar in all 15 countries studied except the Netherlands, where the TT genotype was found to be a genetic risk factor for spina bifida. For the prevention of affected pregnancy every woman planning to conceive has to take folic acid supplements 400 μg a day and the government is asked to take action in implementing food fortification with folic acid in the near future. In conclusion, it is not necessary for Japanese women to undergo genetic screening C677T mutation of the MTHFR gene as a predictive marker for spina bifida prior to pregnancy, because the TT genotype is not a risk factor for having an affected infant.

Association between MTHFR C677T polymorphism and neural tube defect risks: A comprehensive evaluation in three groups of NTD patients, mothers, and fathers

“…The characteristics of all reports on the association between the MTHFRC677T polymorphism and NTDs are shown in Table . The genotype distributions in the controls for all studies were consistent with the Hardy‐Weinberg equilibrium, except for the controls in four studies (De et al, ; Perez et al, ; Shen, ; Kondo et al, ).…”

“…Forty eligible articles were included in this meta‐analysis (listed in Table : Van et al, 1995; Koray et al, ; Molloy et al, ; De et al, ; Christensen et al, ; Shields et al, ; Ubbink et al, ; Lucock et al, ; Yu et al, ; Li et al, ; Martinez et al, 2001; Garcia‐Fragoso et al, ; Arbour et al, ; Perez et al, ; Nitsche et al, ; Parle‐McDermott et al, ; Relton et al, ,b; Sadewa et al, ; Felix et al, ; Dalal et al, ; Munoz et al, ; Shen, ; Candito et al, ; Ceyhan et al, ; Shang et al, ; Wang et al, ; Houcher et al, ; Gao et al, ; Harisha et al, ; Naushad et al, 2010; Eser et al, ; Deb et al, ; Godbole et al, ; Lacasana et al, ; Wei et al, ; Liu et al, ; Kondo et al, ). Some articles may include two or three comparison at the same time.…”

Study of C677T methylene tetrahydrofolate reductase gene polymorphism as a risk factor for neural tube defects

“…(1999), Kondo et al ., Fisk et al ., Naushad and Devi, Behunova et al ., and Nauman et al . [ 24 25 26 27 28 ] Similarly, C677T MTHFR polymorphism was not found to be a risk factor in the studies conducted by Erdogan et al ., Barber et al ., Mornet et al ., and Pardo et al . [ 29 30 31 32 ] Nasri et al ., in their study to find a possible association between MTHFR gene polymorphism and NTD in Tunisian parents found that, TT genotype and T allele in MTHFR C677T significantly decreased the incidence of NTDs in the mother group, but significantly increased this incidence in the father group.…”

“…Some of these studies are tabulated in Table 3. Whereas an association was found to be present between C677T and NTD risk factor in the studies by Relton et [18][19][20][21][22][23] no association was found in the studies conducted by Boduroğlu et [24][25][26][27][28] Similarly, C677T MTHFR polymorphism was not found to be a risk factor in the studies conducted by Erdogan et al, Barber et [29][30][31][32] Nasri et al, in their study to find a possible association between MTHFR gene polymorphism and NTD in Tunisian parents found that, TT genotype and T allele in MTHFR C677T significantly decreased the incidence of NTDs in the mother group, but significantly increased this incidence in the father group. [33] A good deal of interaction occurs between Folate, Vitamin B12, Homocysteine and MTHFR [Figure 7].…”

Loci C677T and A1298C of the methylenetetrahydrofolate reductase gene and the risk of neural tube defects in the Kyrgyz population

“…Большое число исследований посвящено взаимосвязи полиморфизма генов фолатного обмена с пороками развития плода, в частности, с дефектами нервной трубки [5][6][7][8] личии генотипа А1298С риск развития ДНТ повышается в 4,71 раза (OR=4,71; p=0,0079), а при наличии аллеля 1298С -в 2,2 раза (OR=2,20; p=0,041) (табл. 1).…”