Association Of Anticardiolipin Antibody And C677t In Methylenetetrahydrofolate Reductase Mutation In Women With Recurrent Spontaneous Abortions: A New Path To Thrombophilia?

Recurrent spontaneous abortion (RSA) has been associated with venous thrombosis in the mother. Acquired and inherited thrombophilia factors are possible causes. To evaluate the association between thrombogenic factors and recurrent spontaneous abortion. Case-control study. Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. 40 ml of blood was collected from 88 women attending an RSA clinic and 88 fertile women attending a family planning clinic, to evaluate the presence of acquired and inherited thrombophilia factors. Anticardiolipin antibodies (ACA), lupus anticoagulant and deficiencies of proteins C and S and antithrombin III were evaluated by enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. DNA was amplified by the polymerase chain reaction (PCR) to study factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Data were analyzed using odds ratios and a regression model for age adjustment. Fishers exact test was used to evaluate statistical relationships between associated factors and RSA. ACA was detected in 11 women with RSA and one fertile woman. Heterozygous C677T was detected in 59 women with RSA and 35 fertile women. Concomitant presence of ACA and C677T was found in eight women with RSA and no fertile women (p < 0.01). The meaning of the association between C677T mutation in the MTHFR gene and ACA is still not clear. It is possible that an inherited factor that alone would not strongly predispose a woman to thrombosis could, when associated with an acquired factor, start the process and increase the likelihood of thrombosis expression. ACA and C677T in the MTHFR gene are statistically associated with RSA. The association of these two conditions is a new finding in thrombogenic factors and RSA.12315-2

Associação entre anticorpo anticardiolipina e mutação C677T na metileno tetrahidrofolato redutase em mulheres com aborto espontâneo recorrente: um novo caminho na trombofilia?

CONTEXT: Recurrent spontaneous abortion (RSA) has been associated with venous thrombosis in the mother. Acquired and inherited thrombophilia factors are possible causes. OBJECTIVE: To evaluate the association between thrombogenic factors and recurrent spontaneous abortion. TYPE OF STUDY: Case-control study. SETTING: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. METHODS: 40 ml of blood was collected from 88 women attending an RSA clinic and 88 fertile women attending a family planning clinic, to evaluate the presence of acquired and inherited thrombophilia factors. Anticardiolipin antibodies (ACA), lupus anticoagulant and deficiencies of proteins C and S and antithrombin III were evaluated by enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. DNA was amplified by the polymerase chain reaction (PCR) to study factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Data were analyzed using odds ratios and a regression model for age adjustment. Fisher s exact test was used to evaluate statistical relationships between associated factors and RSA. RESULTS: ACA was detected in 11 women with RSA and one fertile woman. Heterozygous C677T was detected in 59 women with RSA and 35 fertile women. Concomitant presence of ACA and C677T was found in eight women with RSA and no fertile women (p < 0.01). DISCUSSION: The meaning of the association between C677T mutation in the MTHFR gene and ACA is still not clear. It is possible that an inherited factor that alone would not strongly predispose a woman to thrombosis could, when associated with an acquired factor, start the process and increase the likelihood of thrombosis expression. CONCLUSIONS: ACA and C677T in the MTHFR gene are statistically associated with RSA. The association of these two conditions is a new finding in thrombogenic factors and RSA.CONTEXTO: O aborto espontâneo recorrente já foi associado a vários fatores etiológicos e à trombose materna. Fatores de trombofilia adquiridos e hereditários podem ser causas destes eventos. OBJETIVO: Avaliar a associação entre fatores de trombofilia e aborto espontâneo recorrente. TIPO DE ESTUDO: Caso-controle. LOCAL: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, São Paulo, Brasil. MÉTODOS: Foram retirados 40 ml de sangue de 88 mulheres com aborto espontâneo recorrente do Ambulatório de Aborto Recorrente e 88 mulheres férteis do Ambulatório de Planejamento Familiar, pareadas por idade e raça, para pesquisar fatores de trombofilia adquiridos e hereditários. O anticorpo anticardiolipina (ACA), anticoagulante lúpico (LA) e a deficiência das proteínas C, S e antitrombina III foram pesquisados por ELISA (enzyme-linkek immunosorbent assay), dRVVT (dilute Russel Viper Venom Time, dRVVT) e métodos coagulométrico e cromogênico. O ácido desoxirribonucléico (DNA) foi amplificado pela técnica de reação em cadeia da polimerase (PCR) para o estudo das mutações fator V de Leiden, G20210A no gene da protrombina e C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR). RESULTADOS: O ACA foi encontrado em 11 mulheres com RSA e em uma mulher fértil [OR 12.4 (IC 95% 1.5 a 98.5)]. A mutação C677T heterozigota foi encontrada em 59 mulheres com RSA e em 35 mulheres férteis [OR 3.1 (IC 95% 1.7 a 5.7)]. A presença concomitante do ACA e da mutação C677T heterozigota foi encontrada em oito mulheres com aborto espontâneo recorrente e em nenhuma mulher fértil (p < 0,01). DISCUSSÃO: O significado da associação entre a mutação heterozigota C677T no gene da MTHFR e o anticorpo anticardiolipina não está claro. Pode-se supor que um fator hereditário que, isolado, não predisporia fortemente um indivíduo à trombose poderia, em associação com um fator adquirido, deflagrar o processo e intensificar a expressão da trombose. CONCLUSÕES: O ACA e a mutação C677T heterozigota no gene da MTHFR apresentaram associação estatística com RSA. A concomitância destas duas alterações é um novo achado no estudo de fatores trombogênicos em aborto espontâneo recorrente.152

Association of anticardiolipin antibody and C677T in methylenetetrahydrofolate reductase mutation in women with recurrent spontaneous abortions: a new path to thrombophilia?

CONTEXT: Recurrent spontaneous abortion (RSA) has been associated with venous thrombosis in the mother. Acquired and inherited thrombophilia factors are possible causes. OBJECTIVE: To evaluate the association between thrombogenic factors and recurrent spontaneous abortion. TYPE OF STUDY: Case-control study. SETTING: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. METHODS: 40 ml of blood was collected from 88 women attending an RSA clinic and 88 fertile women attending a family planning clinic, to evaluate the presence of acquired and inherited thrombophilia factors. Anticardiolipin antibodies (ACA), lupus anticoagulant and deficiencies of proteins C and S and antithrombin III were evaluated by enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. DNA was amplified by the polymerase chain reaction (PCR) to study factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Data were analyzed using odds ratios and a regression model for age adjustment. Fisher’s exact test was used to evaluate statistical relationships between associated factors and RSA. RESULTS: ACA was detected in 11 women with RSA and one fertile woman. Heterozygous C677T was detected in 59 women with RSA and 35 fertile women. Concomitant presence of ACA and C677T was found in eight women with RSA and no fertile women (p < 0.01). DISCUSSION: The meaning of the association between C677T mutation in the MTHFR gene and ACA is still not clear. It is possible that an inherited factor that alone would not strongly predispose a woman to thrombosis could, when associated with an acquired factor, start the process and increase the likelihood of thrombosis expression. CONCLUSIONS: ACA and C677T in the MTHFR gene are statistically associated with RSA. The association of these two conditions is a new finding in thrombogenic factors and RSA