Influence of combined methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase enhancer region (TSER) polymorphisms to plasma homocysteine levels in Korean patients with recurrent spontaneous abortion.
OBJECTIVE
Methylenetetrahydrofolate reductase (MTHFR) mutations known to be associated with hyperhomocysteinemia may be a risk factor for recurrent spontaneous abortion. Recently 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) was reported to affect plasma homocysteine level. We investigated the association between plasma homocysteine level and MTHFR and TSER genotypes.


METHODS
Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutations (C677T and A1298C) were identified by PCR-restriction fragment length polymorphism assay. TSER mutation was analyzed by PCR method.


RESULTS
Average homocysteine level was significantly higher in MTHFR 677TT genotype (9.80+/-3.87 micromol/L) than in MTHFR 677CT (7.04+/-1.99 micromol/L) in MTHFR 677CC genotype (8.14+/-1.74 micromol/L) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). While MTHFR 1298AA showed the highest level, plasma homocysteine levels were not significantly different among MTHFR 1298AA (8.42+/-2.65 micromol/L), 1298AC (6.98+/-2.44 micromol/L) and 1298CC (6.09+/-0.32 micromol/L) (p=0.2058). There was no significant difference among TSER genotypes (2R2R, 8.61+/-1.68 micromol/L; 2R3R, 7.84+/-2.16 micromol/L; 3R3R, 8.05+/-2.81 micromol/L; p=0.9319). Among the combined genotypes of MTHFR C677T and TSER, 677TT-3R3R genotype had the highest homocysteine level (11.47+/-4.66 micromol/L). 1298AA-3R3R had the highest level (8.54+/-3.05 micromol/L) among the combined genotypes of MTHFR A1298C and TSER.


CONCLUSIONS
Although there was no significant difference found among combined genotypes, 3R3R showed elevated homocysteine levels in MTHFR 677TT and 1298AA in Korean patients with unexplained recurrent spontaneous abortion. Thus TSER polymorphism may be a genetic determinant of plasma homocysteine level in Korean patients as well as MTHFR C677T polymorphism.
Institute for Clinical Research, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, 351, Yatap-dong, Bundang-gu, Seongnam, Kyunggi-do, 463-712, South Korea. nkkim@cha.ac.kr
Nam Keun
NK
Kim
Yoon Kyung
YK
Choi
Myung Seo
MS
Kang
Dong Hee
DH
Choi
Sun Hee
SH
Cha
Myung Ok
MO
An
Suman
S
Lee
Mingull
M
Jeung
Jung Jae
JJ
Ko
Doyeun
D
Oh
D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D004742:Enhancer Elements, Genetic; D005260:Female; D005787:Gene Frequency; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000097:blood / Q000235:genetics*
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase