Molecular epidemiology: genetic polymorphisms of the methylenetetrahydrofolate reductase enzime and its relationship with miscarriage

Abstract

O aborto espont??neo (AE) ?? caracterizado como a perda do produto fetal antes de 20 semanas de gesta????o e sua etiologia n??o ?? completamnete esclarecida. In??meros estudos t??m demonstrado que polimorfismos no gene da enzima metilenotetraidrofolato redutase (MTHFR) est??o envolvidos na susceptibilidade ao AE. Dessa forma, o presente trabalho foi realizado com o objetivo de avaliar os polimorfismos 677C>T e 1298A>C do gene da MTHFR e suas associa????es na susceptibilidade ao aborto espont??neo em uma amostra de mulheres do Sul do Brasil em uma abordagem de caso-controle. Noventa e oito mulheres com AE (casos) e duzentas e vinte sete mulheres saud??veis e sem hist??rico de aborto espont??neo (controles) foram estudadas. A genotipagem dos polimorfismos MTHFR677C>T e MTHFR1298A>C foi analisada atrav??s da t??cnica de discrimina????o al??lica com uso de sondas pr??-desenhadas TaqMan?? por PCR em tempo real. Os resultados mostraram que n??o houve diferen??a na distribui????o das frequ??ncias dos alelos e dos gen??tipos dos SNPs MTHFR677C>T e MTHFR1298A>C entre os casos e o grupo controle. Foi observado um aumento do risco de AE em rela????o ao gen??tipo MTHFR1298CC quando comparado ao gen??tipo MTHFR1298AA (RR: 1,13 95%IC: 1,04; 1,23; p=0.02). Al??m disso, a classifica????o do tipo de aborto ?? diferente entre os gen??tipos do polimorfismo MTHFR1298A>C (p = 0,03). No grupo controle, mulheres n??o-carreadoras do alelo 677T apresentam um maior n??mero de gesta????es do que mulheres 677T (p = 0,04). Os resultados apresentados neste trabalho sugerem que o gen??tipo CC do polimorfismo MTHF1298A>C ?? associado ao aumento do risco do AE, entretanto, em nossa popula????o, o polimorfismo MTHFR677C>T n??o est?? envolvido na ocorr??ncia do aborto espont??neo.The spontaneous abortion (SA) is characterized as a loss of fetal product before 20 weeks of gestation and its etiology has not completely understood. Numerous studies have shown that polymorphisms in the gene of the enzyme metilenotetrahydrofolate reductase (MTHFR) are involved in susceptibility to AE. Then, the present study was conducted to evaluate the polymorphisms 677C>T and 1298A>C MTHFR gene and their associations in susceptibility to spontaneous abortion in a sample of women in the South of Brazil in a casecontrol approach. Ninety-eight women with SA (cases) and two hundred and twenty-seven healthy women with no history of miscarriage (controls) were studied. Genotyping of MTHFR677C>T and MTHFR1298A>C polymorphisms were analyzed by allele discrimination with TaqMan?? pre-designed probes in Real Time PCR. The results showed that there was not difference in the distribution of allelic and genotypes frequencies of MTHFR677C>T and MTHFR1298A>C SNPs between cases and control group. It was observed an increase in the risk of SA in relation to genotype THFR1298CC when compared to genotype MTHFR1298AA (RR: 1,13 95%CI: 1,04; 1,23; p=0.02). Moreover, the classification of the type of abortion is different between genotypes of MTHFR1298A>C polymorphism (p = 0.03). In the control group, non-electron carriers of 677T allele have a higher number of pregnancies than women 677T (p = 0.04). The results presented in our work suggests that the CC genotype of polymorphism MTHF1298A > C is associated with increased risk of SA. However, the polymorphism MTHFR677C>T is not involved in the occurrence of miscarriage in studied population