Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida

• Published in: American journal of obstetrics and gynecology Vol. 201; no. 4; pp. 394.e1 - 394.e11
• Main Authors: Martinez, Carla A., MD, Northrup, Hope, MD, Lin, Jone-Ing, MS, Morrison, Alanna C., PhD, Fletcher, Jack M., PhD, Tyerman, Gayle H., MD, Au, Kit Sing, PhD
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-10-2009; Elsevier
• Subjects: Biological and medical sciences; Cystathionine beta-Synthase - genetics; Diseases of the osteoarticular system; Diseases of the spine; folate/homocysteine metabolism genes; Folic Acid - metabolism; Genetic Predisposition to Disease - genetics; Genotype; Gynecology. Andrology. Obstetrics; Humans; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Obstetrics and Gynecology; Polymorphism, Single Nucleotide - genetics; single nucleotide polymorphism; spina bifida; Spinal Dysraphism - genetics; Tetrahydrofolate Dehydrogenase - genetics; Thymidylate Synthase - genetics; folate/homocysteine metabolism genes; single nucleotide polymorphism; spina bifida; Spina bifida; Gene; Malformation; Gynecology; Diseases of the osteoarticular system; Genetics; Spine disease; Single nucleotide polymorphism; Metabolism; Congenital disease; Obstetrics; Folate
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2009.06.042

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. Study Design 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-β-synthase, rs1643649 in dihydrofolate reductase, rs2853533 in thymidylate synthetase, and rs3737965 in methylenetetrahydrofolate reductase was found ( P = .015, .041, .021, and .007 respectively). Conclusion Transmission disequilibrium of SNP alleles in cystathionine-β-synthase, dihydrofolate reductase, methylenetetrahydrofolate reductase, and thymidylate synthetase confers an increased susceptibility to SB.