{{Rsnum
|rsid=1051266
|Gene=SLC19A1
|Chromosome=21
|position=45537880
|Orientation=minus
|GMAF=0.4913
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=SLC19A1
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 16.1 | 55.4 | 28.6
| HCB | 24.8 | 46.7 | 28.5
| JPT | 30.1 | 46.9 | 23.0
| YRI | 49.0 | 39.5 | 11.6
| ASW | 21.1 | 52.6 | 26.3
| CHB | 24.8 | 46.7 | 28.5
| CHD | 18.3 | 54.1 | 27.5
| GIH | 12.9 | 50.5 | 36.6
| LWK | 54.5 | 39.1 | 6.4
| MEX | 17.2 | 36.2 | 46.6
| MKK | 59.6 | 33.3 | 7.1
| TSI | 19.6 | 42.2 | 38.2
| HapMapRevision=28
}}[[rs1051266]] (Arg27Cys, 80G>A) is a snp within [[SLC19A1]] (Solute carrier family 19 (folate transporter), member 1).

{{PMID|19172696}} Cys (A) allele associated with reduced plasma [[folate]]

{{PMID|19650776|OA=1
}}  women with GA and AA genotypes had higher red blood cell folate concentrations, not significantly associated with serum folate or homocysteine levels

{{PMID|18316334}} [[methotrexate]] (antifolate drug) uptake lowest in individuals with GG genotype than those with GA or AA genotypes

{{PharmGKB
|RSID=rs1051266
|Name_s=SLC19A1 (RFC-1): 80A>G, mRNA 199A>G, His27Arg
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15677700
|Annotation=Risk or phenotype-associated allele: SLC19A1 80GG (27Arg/Arg) and GA (27His/Arg)>AA (27His/His) genotypes. Phenotype: A composite pharmacogenetic index (additive from zero to five) was calculated using the following values: ATIC 347CC or TSER*3/*3 or SLC19A1 80GG or SLC19A1 80GA genotypes were valued as 0, ATIC 347CG or TSER*2/*3 or SLC19A1 80AA genotypes were valued as 1, and ATIC 347GG or TSER*2/*2 genotypes were valued as 2. The sum originating from each component (ATIC + TSER + SLC19A1) was calculated and constitutes the pharmacogenetic index for the patient. There was a significant association between smaller pharmacological index and greater number of tender joints (p = 0.002), swollen joints (p = 0.003), greater physician's global assessment of disease activity (p = 0.032), and higher modified Health Assessment Questionnaire (mHAQ) (p = 0.047). Study size: Study population/ethnicity: Significance metric(s): p < 0.05. Type of association: PD; PK; GN; FA
|Drugs=methotrexate
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA165110755
}}

{{PMID Auto
|PMID=20037791
|Title=Genes involved with folate uptake and distribution and their association with colorectal cancer risk
|OA=1
}}

{{PMID Auto
|PMID=20233025
|Title=The SLC19A1 80G&gt;A polymorphism is not associated with male infertility
}}
{{PMID Auto
|PMID=20718043
|Title=Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome
|OA=1
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SLC19A1:Arg27His
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/slc19a1/variant.jsp#ImportantVariantInformationforSLC19A1-Arg27His
|Annotation=Functional effects have been observed in vitro.
|Drugs=methotrexate; raltitrexed
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145160
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SLC19A1:G80A
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15457444; PubMed ID:17410198; PubMed ID:18256692
|Annotation=SNP is associated with the onset of toxicity to methotrexate in patients with psoriasis. SNP was also found in association with clinical response to methotrexate in patients with rheumatoid arthritis.
|Drugs=methotrexate
|Drug Classes=
|Diseases=Arthritis, Rheumatoid; Psoriasis
|Curation Level=Curated
|PharmGKB Accession ID=PA161149190
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SCL19A1:80G>A (His27Arg)
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:12915598
|Annotation=In 53 newly diagnosed patients with childhood acute lymphoblastic leukemia who were treated with two courses of high-dose methotrexate (MTX), no association was found between MTX-induced increases in plasma or cerebrospinal fluid homocysteine levels or MTX-induced toxicity (seizures or thrombosis) based upon the MTHFR 677C>T or RFC (SLC19A1) 80G>A genotypes.
|Drugs=methotrexate
|Drug Classes=
|Diseases=Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165106867
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SCL19A1:80G>A (His27Arg)
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15457444
|Annotation=Rheumatoid arthritis patients taking methotrexate (MTX) >3 months who carry the SLC19A1 (RFC-1) 80AA (27Arg/Arg) genotype showed lower disease activity as assessed by the physician (p < 0.01), less patient-assessed difficulty with physical tasks (p = 0.02), and fewer swollen joints (p = 0.02) compared with carriers 27His-carrying RFC-1 GG and GA genotypes combined; and a pharmacogenetic index of the combined variant alleles for MTX pathway gene variants, TYMS *2, ATIC 347C>G (116Ser), and SLC19A1 (RFC-1) 80G>A (27Arg), was associated with less tender joints (p = 0.012), less swollen joints (p = 0.004), less physician-assessed disease activity (p = 0.0004), and less patient-assessed difficulty with physical tasks (p = 0.001).
|Drugs=methotrexate
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA165106804
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SLC19A1: c.80G>A, p.His27Arg
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15564880
|Annotation=Risk or phenotype-associated allele: TT genotype. Phenotype: Patients with the SLC19A1 80AA genotype were 3.4-fold (p = 0.007) more likely to have methotrexate polyglutamate (MTXPG3-5) levels above the group median compared to those with the SLC19A1 80GG or 80GA genotype. Study size: 226. Study population/ethnicity: Adult rheumatoid arthritis patients from Tennessee and Florida who received low-dose MTX therapy for at least 3 months. Significance metric(s): OR = 3.4; p = 0.007. Type of association: PD, GN
|Drugs=methotrexate
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA165109581
}}

{{PharmGKB
|RSID=rs1051266
|Name_s=SLC19A1: c.80G>A, p.His27Arg
|Gene_s=SLC19A1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:12411325
|Annotation=Risk or phenotype-associated allele: SLC19A1: c.80A, p.His27. Phenotype: Children with acute lymphoblastic leukemia that carry the A allele of rs1051266 (c.80A, p.His27) had significantly worse prognoses than patients with the GG genotype (p = 0.04; OR = 3.0) in event-free survival. Homozygous 80A/A patients had higher plasma levels of methotrexate (p = 0.004) than the other genotype groups. Study size: Subsets of 204 cases. Study population/ethnicity: French Canadian patients of childhood ALL who received high-dose MTX therapy with leucovorin rescue therapy. Significance metric(s): OR = 3.0; p less than 0.05. Type of association: CO; GN
|Drugs=methotrexate
|Drug Classes=
|Diseases=Precursor Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165109618
}}

{{PMID Auto
|PMID=21274745
|Title=Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study
|OA=1
}}

{{PMID Auto
|PMID=17035141
|Title=Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
|OA=1
}}

{{PMID Auto
|PMID=17366837
|Title=Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada.
|OA=1
}}

{{PMID Auto
|PMID=17852831
|Title=Genotyping of the reduced folate carrier-1 c.80G>A polymorphism by pyrosequencing technology: importance of PCR and pre-PCR optimization.
}}

{{PMID Auto
|PMID=18182569
|Title=Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group.
|OA=1
}}

{{PMID Auto
|PMID=18203168
|Title=Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
|OA=1
}}

{{PMID Auto
|PMID=18521744
|Title=BRCA1 promoter methylation is associated with increased mortality among women with breast cancer.
|OA=1
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=18708404
|Title=B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.
|OA=1
}}

{{PMID Auto
|PMID=18842806
|Title=Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.
|OA=1
}}

{{PMID Auto
|PMID=19193698
|Title=Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.
|OA=1
}}

{{PMID Auto
|PMID=19252927
|Title=Bladder cancer SNP panel predicts susceptibility and survival.
|OA=1
}}

{{PMID Auto
|PMID=19376481
|Title=One-carbon metabolism and breast cancer: an epidemiological perspective.
|OA=1
}}

{{PMID Auto
|PMID=19493349
|Title=118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.
|OA=1
}}

{{PMID Auto
|PMID=19706844
|Title=Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.
}}

{{PMID Auto
|PMID=20472929
|Title=Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis.
}}

{{PMID Auto
|PMID=20511665
|Title=Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=20661649
|Title=A80G polymorphism of reduced folate carrier 1 (RFC1) gene and head and neck squamous cell carcinoma etiology in Brazilian population.
}}

{{PMID Auto
|PMID=20890936
|Title=Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population.
}}

{{GET Evidence
|gene=SLC19A1
|aa_change=His27Arg
|aa_change_short=H27R
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1051266
|overall_frequency_n=5410
|overall_frequency_d=10724
|overall_frequency=0.504476
|n_genomes=38
|n_genomes_annotated=0
|n_haplomes=52
|n_articles=5
|n_articles_annotated=5
|in_pharmgkb=Y
|pph2_score=0.002
|nblosum100=1
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23148635
|Title=Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients
}}

{{PMID Auto
|PMID=24554143
|Title=Serum Folic Acid and RFC A80G Polymorphism in Alzheimer's Disease and Vascular Dementia
}}

{{PMID Auto
|PMID=22021659
|Title=Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.
|OA=1
}}

{{PMID Auto
|PMID=22859359
|Title=ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis.
}}

{{PMID Auto
|PMID=22890010
|Title=Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.
}}

{{PMID Auto
|PMID=24782176
|Title=RFC1 80G&gt;A Is a Genetic Determinant of Methotrexate Efficacy in Rheumatoid Arthritis: A Human Genome Epidemiologic Review and Meta-Analysis of Observational Studies
}}

{{PMID Auto
|PMID=24917213
|Title=Interaction between the SLC19A1 Gene and maternal first trimester fever on offspring neural tube defects
}}

{{PMID Auto
|PMID=25124723
|Title=SLC19A1, SLC46A1 and SLCO1B1 Polymorphisms As Predictors Of Methotrexate-Related Toxicity In Portuguese Rheumatoid Arthritis Patients
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}