{{Rsnum
|rsid=70991108
|geno1=(-;-)
|geno2=(-;TGGCGCGTCCCGCCCAGGT)
|geno3=(TGGCGCGTCCCGCCCAGGT;TGGCGCGTCCCGCCCAGGT)
|Orientation=plus
|Chromosome=5
|position=80654344
|Gene=DHFR
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Gene_s=DHFR,MSH3
}}[[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|19022952|OA=1
}} 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|19648163|OA=1
}} 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

{{PharmGKB
|RSID=rs70991108
|Name_s=DHFR:19bp deletion, DHFR 19-bp deletion
|Gene_s=DHFR, MSH3
|Feature=
|Evidence=PubMed ID:17413111
|Annotation=Risk or phenotype-associated allele: del/del Phenotype: In multivitamin users, the del/del genotype was associated with increased risk for breast cancer. Study size: 536 Study population/ethnicity: Multivitamin users in the Long Island Breast Cancer Study Project; women; Significance metric(s): OR = 1.52 (95% CI = 1.08, 2.13) Type of association: CO
|Drugs=
|Drug Classes=MULTIVITAMINS, PLAIN
|Diseases=Breast Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA165223223
}}

{{PharmGKB
|RSID=rs70991108
|Name_s=DHFR c.86 + 60_78; DHFR:19bp deletion in intron 1;
|Gene_s=DHFR, MSH3
|Feature=
|Evidence=PubMed ID:18247058
|Annotation=Risk or phenotype-associated allele: del/del Phenotype: Women with the del/del genotype had increased serum and red blood cell folate concentrations. Study size: 197 Study population/ethnicity: Females from the Young Hearts Study; 20-26 years old; Northern Ireland Significance metric(s): p = 0.02 (serum folate); p = 0.16 (red blood cell folate) Type of association: PD
|Drugs=folic acid
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165223222
}}

{{PharmGKB
|RSID=rs70991108
|Name_s=DHFR 19 bp deletion
|Gene_s=DHFR, MSH3
|Feature=
|Evidence=PubMed ID:19648163
|Annotation=Risk or phenotype-associated allele: del Phenotype: Carriage of the deletion allele was associated with a 2.42-fold increased risk of hepatic toxicity to methotrexate. Study size: 122 Study population/ethnicity: Caucasian; Italy; Adults aged 18-80 years; 83% had B-ALL and 17% had TALL Significance metric(s): p = 0.052 Type of association: TOX
|Drugs=methotrexate
|Drug Classes=
|Diseases=Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165223224
}}
{{PMID Auto
|PMID=22005284
|Title=Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability
}}
{{PMID Auto
|PMID=22648968
|Title=Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake
|OA=1
}}{{PMID Auto
|PMID=23053953
|Title=Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer.
}}