Abnormal folic acid-homocysteine metabolism as maternal risk factors for Down syndrome in Japan.
BACKGROUND
Japan has been considered as "a folate sufficient area", since traditional Japanese food contains an adequate amount of folic acid. However, the recent westernized food style of young Japanese mothers may affect the intake of folic acid among them. This food style may contribute to the occurrence of Down syndrome, which has proved to be linked to abnormal folate and homocysteine metabolisms.


OBJECTIVE
To preliminarily evaluate the levels of folic acid,homocysteine and other relevant factors which are associated with folate metabolism, among Japanese women who had pregnancies affected by Down syndrome.


METHODS
Blood samples from 31 women who had pregnancies affected by Down syndrome (DS) were obtained. 60 age-matched control blood samples were also obtained from mothers who had not experienced miscarriages or abnormal pregnancies (CONT). Plasma homocysteine and serum folic acid, vitamin B12, and B6 were measured and compared between DS and CONT. Furthermore, the frequency of MTHFR polymorphism (C677T) was also investigated.


RESULTS
Plasma levels of homocysteine were significantly increased in DS mothers (p = 0.004). In contrast, serum levels of folic acid were significantly decreased in DS mothers (p = 0.0001). There were no significant differences in the vitamin B12 and B6 levels between DS and CONT. Also, the frequency of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) homozygous polymorphism showed no differences between DS and CONT.


CONCLUSIONS
Different levels of serum folic acid and plasma homocysteine between both groups may contribute to the occurrence of Down syndrome even in Japan. Although there was no significant difference in the frequency of MTHFR polymorphism between the groups, probably because of an inadequate number of samples, further studies may contribute to the understanding of the occurrence of Down syndrome in Japan.
Takamura
Noboru
N
Dept. of Public Health, Nagasaki University, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. takamura@net.nagasaki-u.ac.jp.
Kondoh
Tatsuro
T
Ohgi
Syohei
S
Arisawa
Kokichi
K
Mine
Mariko
M
Yamashita
Shunichi
S
Aoyagi
Kiyoshi
K
D000328:Adult; D004314:Down Syndrome / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007564:Japan / Q000453:epidemiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy / Q000097:blood* / Q000378:metabolism; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12