Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in nulliparous women complicated with preeclampsia

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Abstract
Objective: To determine the prevalence of C677T and A1298C Single-nucleotide polymorphisms (SNPs) of the MTHFR gene in nulliparous women complicated with preeclampsia (PE). Methods: One hundred fifty gestations complicated with PE and their corresponding controls without the disease were recruited for the genotyping of C677T and A1298C polymorphisms of the MTHFR gene using restriction fragment length polymorphism polymerase chain reaction. Secondarily, homocysteine (HCy) plasma levels were measured in preeclamptic women displaying the CC genotype of the A1298C polymorphism (homozygous) and compared to HCy levels determined among controls with the normal AA genotype for the A1298C variant. Results: Only the mutant CC genotype of the A1298C polymorphism was associated to higher risk of presenting PE, as frequency of this genotype was significantly higher among cases than controls (15.3% versus 0.7%, p < 0.05). All PE women with a neck circumference ≥32 cm presented the mutant CC A1298C polymorphism as compared to none among preeclamptics with a lower neck circumference (p = 0.0001). Women with the mutant CC A1298C SNP displayed higher plasma HCy levels as compared to controls with normal AA A1298C genotype (8.4 ± 2.6 versus 7.5 ± 2.7 mmoL/L p = 0.04). Conclusion: Prevalence of the CC mutant genotype of the A1298C polymorphism was higher among PE women. This mutation among PE women was related to increased neck circumference and higher HCy levels. Future research should aim at linking these gestational findings with obesity and cardiovascular risk.

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