Roles of Methylenetetrahydrofolate Reductase C677T Polymorphism in Repeated Pregnancy Loss

Abstract

Congenital thrombophilia in repeated pregnancy lost (RPL) has been noted for years. Methylenetetrahydrofolate reductase (MTHFR) gene is an interesting gene, mentioned for its possible roles in RPL. There is considerable controversy regarding the clinical role of MTHFR C677T polymorphism as a risk factor of RPL. Here, a summative analysis is performed on the recent previous reports on the MTHFR C677T and its correlation to RPL. The metanalysis was performed to assess the correlation between the pattern of MTHFR C677T polymorphism and RPL. From available eight case-control studies, 752 patients and 625 controls are evaluated. The overall frequencies of 4G allele for the patients and controls are 31.5 and 33.5, respectively. According to this study, 53.1% of subjects with T allele have RLP while 55.3% of subjects without T allele have RLP. From overall risk estimation, the subjects with T alleles have 0.96 times lower risk to RLP. According to this analysis, the pattern of MTHFR C677T polymorphism might not represent a useful marker of increased risk for RPL. In addition, there was no association between pattern of MTHFR C677T polymorphism and ethnicity of the patients in this study.

Keywords

Repeated pregnancy loss Polymorphism Methylenetetrahydrofolate reductase

References

Yamada H , Kato EH , Kobashi G , et al. Recurrent pregnancy loss: Etiology of thrombophilia. Semin Thromb Hemost 2001;27:121.

Schwahn B , Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: Clinical consequences. Am J Pharmacogenomics 2001;1:189.

Nakai K , Itoh C , Nakai K , et al. Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and the incidence of CAD. Am J Cardiovasc Drugs 2001;1:353.

Sharp L , Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: A Huge review. Am J Epidemiol 2004;159:423.

Wang XP , Lin QD , Ma ZW , Zhao AM . C677T and A1298C mutation of the methylenetetrahydrofolate reductase gene in unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi 2004;39:238.

Pauer HU , Voigt-Tschirschwitz T , Hinney B , et al. Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand 2003;82:942.

Kumar KS , Govindaiah V , Naushad SE , et al. Plasma homocysteine levels correlated to interactions between folate status and methylene tetrahydrofolate reductase gene mutation in women with unexplained recurrent pregnancy loss. J Obstet Gynaecol 2003;23:55.

Carp H , Salomon O , Seidman D , et al. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod 2002;17:1633.

Unfried G , Griesmacher A , Weismuller W , et al. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol 2002;99:614.

10.

Foka ZJ , Lambropoulos AF , Saravelos H , et al. Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod 2000;15:458.

11.

Brenner B , Sarig G , Weiner Z , et al. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost 1999;82:6.

12.

Holmes ZR , Regan L , Chilcott I , Cohen H. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol 1999;105:98.