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rs70991108

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
({{{allele1}}};{{{allele2}}}) 0 common in clinvar
(-;-) 1.5 high folic acid intake leads to high unmetabolized folic acid circulating levels, whereas low intake leads to low RBC folate
(-;TGGCGCGTCCCGCCCAGGT) some variation in folic acid metabolism
(TGGCGCGTCCCGCCCAGGT;TGGCGCGTCCCGCCCAGGT) normal
ReferenceGRCh38 38.1/141
Chromosome5
Position80654344
GeneDHFR, MSH3
is asnp
is mentioned by
dbSNPrs70991108
ebirs70991108
HLIrs70991108
Exacrs70991108
Varsomers70991108
Maprs70991108
PheGenIrs70991108
hapmaprs70991108
1000 genomesrs70991108
hgdprs70991108
ensemblrs70991108
gopubmedrs70991108
geneviewrs70991108
scholarrs70991108
googlers70991108
pharmgkbrs70991108
gwascentralrs70991108
openSNPrs70991108
23andMers70991108
23andMe allrs70991108
SNP Nexus

SNPshotrs70991108
SNPdbers70991108
MSV3drs70991108
GWAS Ctlgrs70991108
Max Magnitude1.5
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.

[PMID 19022952OA-icon.png] 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).

[PMID 19648163OA-icon.png] 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
  • [PMID 17486595]: suggested that the del/del genotype actually reduced risk for spina bifida
  • [PMID 17336564]: found no connection whatsoever between the del/del genotype and spina bifida risk




[PMID 22005284] Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability

[PMID 22648968OA-icon.png] Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake [PMID 23053953] Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer.

ClinVar
Risk rs70991108(TGGCGCGTCCCGCCCAGGT;TGGCGCGTCCCGCCCAGGT)
Alt rs70991108(TGGCGCGTCCCGCCCAGGT;TGGCGCGTCCCGCCCAGGT)
Reference rs70991108(;)
Significance Unknown
Disease Gastrointestinal stromal tumor
Variation info
Gene DHFR MSH3
CLNDBN Gastrointestinal stromal tumor
Reversed 0
HGVS NC_000005.9:g.79950163_79950164insTGGCGCGTCCCGCCCAGGT
CLNSRC ClinVar University of Bologna
CLNACC RCV000144918.1,



[PMID 26269242] The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake