Estudo de polimorfismos em genes relacionados ao metabolismo do ácido fólico e sua associação com o desenvolvimento de fendas orais não-sindrômicas

摘要

The congenital facial clefts are characterized by incomplete formation ofthe structures that separate the oral and nasal cavity. It is known that severalenvironmental and genetic factors are involved in its development, among these,polymorphisms associated with folic acid metabolism have been investigated. In thissense, the objective was to observe the frequency of polymorphisms C677T andA1298C methylenetetrahydrofolate reductase gene (MTHFR), methionine synthaseA2756G of (MTR), A66G of methionine synthase reductase (MTRR) A80G and thereduced folate carrier (RFC1) in patients with non-syndromic oral clefts, trying to matchthem with their development. Methods: We studied 140 patients with non-syndromicoral clefts and their mothers and 175 control subjects with their mothers, whounderwent a questionnaire to obtain family information. Were collecting blood for DNAextraction from patients and their mothers to identify the genotypes of both by PCRRFLP,in addition to carrying out the determination of glucose, AST, ALT and serumcreatinine, folic acid and vitamin B12 Serum and plasma homocysteine, and thehemogram. Results: Most patients have cleft lip and palate (55.8%), followed byisolated cleft palate (24.2%) and cleft lip (20%). Regarding gender, 62% of patientswere male and 48% female and, after subdivision of the type of screwdriver accordingto sex was found a prevalence of males in the cracks of the type lip and palate (69 %)and lip (69.2%) and in the case of cleft palate was a female predominance (59%). Theaverage concentration of serum folate in the group of mothers of cleft patients wassignificantly lower (13.8 ± 2.4 ng / mL) compared with the group of mothers of controlsubjects (18.8 ± 3.4 ng / mL) This was also observed for the group of cleft children ascompared to controls, the dosage of folic acid had a significant difference with values of15.6 ± 0.6 (ng / mL) and 17.9 ± 0.6 (ng / mL), respectively. For the biochemicalmeasurements of glucose, AST, ALT and creatinine were not statistically different, norwas observed for haematological parameters performed. In assessing the frequency ofpolymorphisms C677T and A1298C MTHFR, A2756G MTR, MTRR A66G and A80Gof the RFC1 there was no statistically significant difference in genotype distributionbetween cases and controls both for mothers and in the cleft. Conclusion: Although notobserved association of polymorphisms with the development of cracks, the decrease inserum folate in the group of cleft patients and their mothers may reflect a disturbance inthe metabolism of this metabolite, necessitating further studies such as studiesmethylation and expression to further elucidate the involvement of folate in thedevelopment of oral clefts