Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida.
OBJECTIVE
We tested putative functional single nucleotide polymorphisms (SNPs) in genes that regulate the folate/homocysteine metabolism pathway for their contribution to spina bifida (SB) susceptibility.


METHODS
The study consisted of 610 unrelated simplex SB patient families. Genotypes of 46 SNPs located in the coding sequence or promoter region of 11 genes were investigated. Associations between transmission of alleles and SB in the offspring were examined using the reconstruction combined transmission disequilibrium test.


RESULTS
Significant association of SNP rs5742905 in cystathionine-beta-synthase, rs1643649 in dihydrofolate reductase, rs2853533 in thymidylate synthetase, and rs3737965 in methylenetetrahydrofolate reductase was found (P = .015, .041, .021, and .007 respectively).


CONCLUSIONS
Transmission disequilibrium of SNP alleles in cystathionine-beta-synthase, dihydrofolate reductase, methylenetetrahydrofolate reductase, and thymidylate synthetase confers an increased susceptibility to SB.
Martinez
Carla A
CA
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center, Houston, TX, USA.
Northrup
Hope
H
Lin
Jone-Ing
JI
Morrison
Alanna C
AC
Fletcher
Jack M
JM
Tyerman
Gayle H
GH
Au
Kit Sing
KS
D003541:Cystathionine beta-Synthase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016135:Spinal Dysraphism / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D003541:Cystathionine beta-Synthase
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