Genetic polymorphisms and Down syndrome risk in Brazilians

http://www.ncbi.nlm.nih.gov/pubmed/22339736

Genet Test Mol Biomarkers. 2012 Feb 17. [Epub ahead of print]
BHMT G742A and MTHFD1 G1958A Polymorphisms and Down Syndrome Risk in the Brazilian Population.
Zampieri BL, Biselli JM, Goloni-Bertollo EM, Pavarino EC.
Source
Department of Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM) , São José do Rio Preto, SP, Brazil .
Abstract
Background:
Mechanisms underlying meiotic nondisjunction are poorly understood. Attempts to elucidate the causes of Down syndrome (DS) have analyzed the relationship between polymorphism in folate metabolism and DS. Aim: The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated.

Methods:
Blood samples were collected from a total of 86 DS mothers and from 161 control mothers. The investigation of the MTHFD1 G1958A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by real-time PCR for the BHMT G742A polymorphism.

Results:
The median maternal age of case mothers (30.40; 12.9-46.3 years) was significantly higher (p<0.0005) than in the control group (26.60; 15.4-57.9 years). The frequency of BHMT variant genotypes was significantly lower in DS mothers compared with controls (p=0.047). A significant decreased risk for BHMT 742 AA genotype (odds ratio [OR]=0.30; 95% confidence interval [CI]: 0.10-0.93; p=0.037) was observed. Moreover, when the dominant model was applied (BHMT 742GA or 7428AA versus 742GG), there was also a significant decrease in DS risk (OR=0.58; 95% CI: 0.37-0.98; p=0.042). MTHFD1 G1958A genotype frequencies were not significantly altered in DS mothers (p=0.206).

Conclusions:
Our study suggests that the polymorphism BHMT G742A may modulate the DS risk in Brazilian mothers.