Infant C677T MTHFR polymorphism and severe mental retardation.
BACKGROUND
We investigated whether infants with homozygous genotype TT of the MTHFR gene were at increased risk of severe mental retardation.


METHODS
One hundred children with severe mental retardation (cases) were investigated from a large geographic-based study of infants born in California in 1992-1993. Cases were compared to 743 randomly selected nonmalformed control infants born in California during 1987-1991. DNA was extracted from newborn screening filter papers. Cases and controls were genotyped TT if homozygous for the MTHFR C677T allele, CT if heterozygous for the C677T allele, and CC if homozygous for the C677 (wild type) allele.


RESULTS
Overall, case and control infants had similar percentages of TT and CT genotypes. Percentages between cases and controls differed somewhat across race/ethnic groups. Elevated ORs of 1.9 (95% CI: 0.7-5.0) and 2.6 (95% CI: 1.1-5.8) were observed for the TT and CT genotypes, respectively, among Hispanic children. Observed results were not substantially altered for analyses that removed 41 case children who also had structural birth defects.


CONCLUSIONS
Folate-related mechanisms are important to investigate for etiologies of birth defects, and such lines of inquiry may be revealing for mental retardation given the relationships between mental retardation and birth defects and potential relationships between folate, DNA methylation, and mental retardation.
Shaw
Gary M
GM
California Birth Defects Monitoring Program, Berkeley, California 94710, USA. gsh@cbdmp.org
Jelliffe-Pawlowski
Laura
L
Nelson
Verne
V
Zhu
Huiping
H
Harris
John A
JA
Finnell
Richard H
RH
D000483:Alleles; D000013:Congenital Abnormalities / Q000209:etiology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)