Polymorphisms in genes MTHFR, MTR and MTRR are not risk factors for cleft lip/palate in South Brazil

A.P.C Brandalize,I Roisenberg,L Schüler-Faccini,E Bandinelli,T.M Félix,J.B Borba

doi:10.1590/s0100-879x2006005000112

Abstract

Non-syndromic cleft lip and palate (CL/P) occurs due to interaction between genetic and environmental factors. Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway. Because of the involvement of MTHFR, MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for CL/P, we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study. The analyses involved 114 non-syndromic phenotypically white children with clefts (case) and 110 mothers, and 100 non-affected (control) children and their mothers. The polymorphisms 677C>T of MTHFR, 2756A>G of MTR, and 66A>G of MTRR genes were analyzed by PCR-RFLP. Allelic frequencies did not differ from other studies conducted on white populations for MTHFR 677T allele (0.35) and for MTR 2756G allele (0.17), but MTRR 66G allele frequency (0.35) was lower than observed elsewhere. The genotypic distribution of the 677C>T polymorphisms under study did not show significant differences between CL/P patients, their mothers and controls. These results suggest that the alterations of folate metabolism related to these polymorphisms are not involved in clefting in the population under study.

Highlights

Craniofacial anomalies, cleft lip/palate (CL/P), are among the most common birth defects
Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway
Because of the involvement of methylenetetrahydrofolate reductase (MTHFR), MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for cleft lip and palate (CL/P), we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study

Summary

Introduction

Craniofacial anomalies, cleft lip/palate (CL/P), are among the most common birth defects. They affect approximately 1 in 700 births, a frequency which may differ according to the geographical region and socio-economic level. The CL/ P have a great clinical impact, demanding surgical, odontologic, phonoaudiologic, and psychological care during childhood and adolescence [1]. Their complex etiology involves genetic and environmental factors [2]. The metabolism of homocysteine begins with the intake of folic acid through the diet. Folic acid is rapidly reduced to its active form tetrahydrofolate which turns to 5,10-

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