Rs70991108

rs70991108 is a polymorphism consisting of a 19-bp deletion in the first intron of the dihydrofolate reductase DHFR gene. The wild-type (non-deletion) allele is a bit more common than the deletion allele in most populations. Several studies have linked this SNP to alterations in folic acid (and folate) metabolism.

A study of 1,215 subjects from the Framingham Offspring Study concluded that rs70991108 influences the prevalence of circulating folic acid levels. Specifically, folic acid intake over 500ug/d led to high circulating (unmetabolized) folic acid levels in subjects homozygous for the deletion genotype. When folic acid intake was under 250ug/d, the deletion/deletion homozygotes had lower RBC folate (732.2 nmol/L) compared with the non-deletion genotype (844.4 nmol/L).

A 2-year follow-up study of 122 newly diagnosed patients with acute lymphoblastic leukemia (ALL) found that carriers of a rs70991108 deletion allele were at increased risk for hepatic toxicity from methotrexate treatment. Hepatic toxicity was increased ~2x and ~4.6x for heterozygous and homozygous rs70991108 deletion genotypes, respectively (p=0.05). If a carrier of a rs70991108 deletion allele was also a carrier of a rs1801133(T) allele, the risk for hepatic toxicity was even higher (odds ratio 6.8, p=0.018).

Studies have also looked for connections between this SNP and the risk of having a baby born with spina bifida, but the results are inconsistent between studies:


 * [PMID 14735580, PMID 15755837]: suggested the del/del genotype increased risk for spina bifida and pre-term delivery
 * : suggested that the del/del genotype actually reduced risk for spina bifida
 * : found no connection whatsoever between the del/del genotype and spina bifida risk


 * is_associated_with_disease::Leukemia
 * is_associated_with_disease::Intellectual disability
 * is_associated_with_disease::Spina bifida
 * is_associated_with_disease::Breast cancer