SLC19A1 H27R - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

SLC19A1 H27R

(SLC19A1 His27Arg)


Short summary

 

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr21:46957794: 50.4% (5410/10724) in EVS
  • C @ chr21:45782221: 51.6% (66/128) in GET-Evidence
  • Frequency shown in summary reports: 50.4% (5410/10724)

Publications
 

Laverdière C, Chiasson S, Costea I, Moghrabi A, Krajinovic M. Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood. 2002 Nov 15;100(10):3832-4. PubMed PMID: 12411325.

 

Kishi S, Griener J, Cheng C, Das S, Cook EH, Pei D, Hudson M, Rubnitz J, Sandlund JT, Pui CH, Relling MV. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J Clin Oncol. 2003 Aug 15;21(16):3084-91. PubMed PMID: 12915598.

 

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004 Sep;50(9):2766-74. PubMed PMID: 15457444.

 

Dervieux T, Kremer J, Lein DO, Capps R, Barham R, Meyer G, Smith K, Caldwell J, Furst DE. Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics. 2004 Nov;14(11):733-9. PubMed PMID: 15564880.

 

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Caldwell J, Kremer J. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis. 2005 Aug;64(8):1180-5. Epub 2005 Jan 27. PubMed PMID: 15677700; PubMed Central PMCID: PMC1755602.

 

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het C @ chr21:46957794

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het C @ chr21:46957794

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het C @ chr21:46957794

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het C @ chr21:46957794

 

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het C @ chr21:46957794

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het C @ chr21:46957794

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het C @ chr21:46957794

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het C @ chr21:46957794

 

hu34D5B9 - CGI sample GS01173-DNA_C07 from PGP sample 92161424
het C @ chr21:46957794

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het C @ chr21:46957794

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
hom C @ chr21:46957794

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het C @ chr21:46957794

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
hom C @ chr21:46957794

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom C @ chr21:46957794

 

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
hom C @ chr21:46957794

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
hom C @ chr21:46957794

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het C @ chr21:46957794

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
hom C @ chr21:46957794

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het C @ chr21:46957794

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr21:46957794

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
hom C @ chr21:46957794

 

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
hom C @ chr21:46957794

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr21:46957794

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
hom C @ chr21:46957794

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het C @ chr21:46957794

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr21:46957794

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het C @ chr21:46957794

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom C @ chr21:46957794

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
hom C @ chr21:46957794

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
hom C @ chr21:46957794

 

GS06985 - var-GS06985-1100-36-ASM
het C @ chr21:45782222

 

GS07357 - var-GS07357-1100-36-ASM
het C @ chr21:45782222

 

GS10851 - var-GS10851-1100-36-ASM
hom C @ chr21:45782222

 

GS18501 - var-GS18501-1100-36-ASM
hom C @ chr21:45782222

 

GS18508 - var-GS18508-1100-36-ASM
het C @ chr21:45782222

 

GS18517 - var-GS18517-1100-36-ASM
het C @ chr21:45782222

 

GS18526 - var-GS18526-1100-36-ASM
het C @ chr21:45782222

 

GS18537 - var-GS18537-1100-36-ASM
het C @ chr21:45782222

 

GS18558 - var-GS18558-1100-36-ASM
het C @ chr21:45782222

 

GS18940 - var-GS18940-1100-36-ASM
hom C @ chr21:45782222

 

GS18942 - var-GS18942-1100-36-ASM
hom C @ chr21:45782222

 

GS18956 - var-GS18956-1100-36-ASM
het C @ chr21:45782222

 

GS19020 - var-GS19020-1100-36-ASM
het C @ chr21:45782222

 

GS19129 - var-GS19129-1100-36-ASM
het C @ chr21:45782222

 

GS19648 - var-GS19648-1100-36-ASM
hom C @ chr21:45782222

 

GS19649 - var-GS19649-1100-36-ASM
het C @ chr21:45782222

 

GS19669 - var-GS19669-1100-36-ASM
het C @ chr21:45782222

 

GS19670 - var-GS19670-1100-36-ASM
het C @ chr21:45782222

 

GS19700 - var-GS19700-1100-36-ASM
het C @ chr21:45782222

 

GS19701 - var-GS19701-1100-36-ASM
het C @ chr21:45782222

 

GS19703 - var-GS19703-1100-36-ASM
hom C @ chr21:45782222

 

GS19704 - var-GS19704-1100-36-ASM
het C @ chr21:45782222

 

GS19735 - var-GS19735-1100-36-ASM
hom C @ chr21:45782222

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr21:45782222

 

GS20502 - var-GS20502-1100-36-ASM
hom C @ chr21:45782222

 

Other external references
 

    dbSNP
  • rs1051266
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma]
    [methotrexate]
    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.
    www.ncbi.nlm.nih.gov/pubmed/12915598
  • [Arthritis, Rheumatoid]
    [methotrexate]
    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).
    www.ncbi.nlm.nih.gov/pubmed/15457444
  • [Arthritis, Rheumatoid]
    [methotrexate]
    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
    www.ncbi.nlm.nih.gov/pubmed/15564880
  • [Precursor Cell Lymphoblastic Leukemia-Lymphoma]
    [methotrexate]
    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
    www.ncbi.nlm.nih.gov/pubmed/12411325
  • [Arthritis, Rheumatoid]
    [methotrexate]
    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
    www.ncbi.nlm.nih.gov/pubmed/15677700
    PolyPhen-2
  • Score: 0.002 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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