A systematic review and meta-analysis of the association between polymorphisms in maternal genes involved in folate metabolism and the birth of individuals with Down Syndrome

• Grant number: 12/04664-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2012
• End date: June 30, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Erika Cristina Pavarino
• Grantee: Erika Cristina Pavarino
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). São José do Rio Preto , SP, Brazil
• City of the host institution: São José do Rio Preto

Abstract

Down Syndrome is the most common cause mental deficiency of genetic etiology, present in approximately one case per 600-700 births, making it the most common condition of aneuploidy compatible with life. In 95% of cases, is attributed to free trisomy of chromosome 21 resulting from maternal meiotic nondisjunction.It is well established that advanced maternal age is a risk factor for non-disjunction, however other etiological factors independent of maternal age are also related to the occurrence of Down syndrome. Among these factors, is hypomethylation of centromeric DNA as a consequence of abnormal folate metabolism, and polymorphisms in genes encoding enzymes involved in metabolism, have been suggested as maternal risk factors for the syndrome. Genetic polymorphisms may alter the resulting products of the folate metabolic pathway and result in DNA hypomethylation, genomic instability and reduced DNA repair capacity. Studies investigating the association between genetic polymorphisms involved in folate metabolic pathway and Down syndrome, report contradictory or inconclusive results. Therefore, the aim of this study is to determine, through systematic review and meta-analysis, the presence of polymorphisms in folate metabolic pathway have genetic risk factors for birth mothers of children with Down syndrome, based on best available evidence in literature. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

VICTORINO, D. B.; GODOY, M. F.; GOLONI-BERTOLLO, E. M.; PAVARINO, E. C.. Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: increased susceptibility in women carriers of the MTHFR 677T allele. MOLECULAR BIOLOGY REPORTS, v. 41, n. 8, p. 5491-5504, AUG 2014. (12/04713-9, 12/04664-8)