MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae.

This study examined the relationship between folate/homocysteine-related genetic polymorphisms: MTHFD1 1958G --> A (R653Q), MTHFR 677C --> T (A222V), MTHFR 1298A --> C (E429A), and risk of severe abruptio placentae. We genotyped 62 women with a pregnancy history complicated by severe abruptio placentae and 184 control pregnancies. Analysis of the MTHFD1 1958G --> A (R653Q) polymorphism showed increased frequency of the 'QQ' homozygote genotype in pregnancies affected by severe abruptio placentae compared to control pregnancies (odds ratio 2.85 (1.47-5.53), P = 0.002). In contrast to previous reports, the MTHFR polymorphisms 677C --> T (A222V) and 1298A --> C (E429A) were not associated with abruptio placentae risk in our cohort, when analyzed either independently or in combination. We conclude that women who are 'QQ' homozygote for the MTHFD1 1258G --> A (R653Q) polymorphism are almost three times more likely to develop severe abruptio placentae during their pregnancy than women who are 'RQ' or 'RR.'