TGFB1 R25P - GET-Evidence

Curation:
Currentness:

TGFB1 R25P

(TGFB1 Arg25Pro)


Short summary

This variant in a growth factor gene is associated with variation in TGFB1 levels; this has been associated with various pathogenic and some protective effects, including: more hepatic fibrosis progression in hep C patients, lower risk of cleft palate, anticorrelation with longevity, higher risk of myocardial infarction and lower risk of hypertension.

Variant evidence
Computational -
Functional -
Case/Control 3

Unclear overall effect, many different phenotypes implicated protectively or pathogenically.

See Cambien F et al. 1996 (8901839), Tag CG et al. 2003 (14596813), Stoll C et al. 2004 (15212689), Carrieri G et al. 2004 (15569360).

Familial

No familial evidence.

 
Clinical importance
Severity 2

Unclear overall effect

Treatability

no standard treatment

Penetrance 2

Multiple associations, presumed low penetrance

 

Impact

Low clinical importance, Uncertain pathogenic

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

other

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr19:41858876: 4.9% (487/9962) in EVS
  • G @ chr19:46550715: 3.6% (4/110) in GET-Evidence
  • Frequency shown in summary reports: 4.9% (487/9962)

Publications
 

Cambien F, Ricard S, Troesch A, Mallet C, Générénaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O. Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension. 1996 Nov;28(5):881-7. PubMed PMID: 8901839.

These authors found apparently inconsistent results (as they themselves note), with the Pro25 allele associated with an increased risk of myocardial infarction and a reduced risk of hypertension.

Tag CG, Mengsteab S, Hellerbrand C, Lammert F, Gressner AM, Weiskirchen R. Analysis of the transforming growth factor-beta1 (TGF-beta1) codon 25 gene polymorphism by LightCycler-analysis in patients with chronic hepatitis C infection. Cytokine. 2003 Dec 7;24(5):173-81. PubMed PMID: 14596813.

This variant is shown to cause variation in TGFB1 levels, and in chronic hepatitis C patients was shown to associate with progression of hepatic fibrosis.

Stoll C, Mengsteab S, Stoll D, Riediger D, Gressner AM, Weiskirchen R. Analysis of polymorphic TGFB1 codons 10, 25, and 263 in a German patient group with non-syndromic cleft lip, alveolus, and palate compared with healthy adults. BMC Med Genet. 2004 Jun 22;5:15. PubMed PMID: 15212689; PubMed Central PMCID: PMC441379.

In a study looking at cleft lip, alveolus, and palate (CLP), only 2/60 patients with CLP (3.3%) carried the Arg25Pro; in the controls 16.7% had Arg25Pro (10/60; p < 0.035), suggesting this variant is protective for CLP.

Carrieri G, Marzi E, Olivieri F, Marchegiani F, Cavallone L, Cardelli M, Giovagnetti S, Stecconi R, Molendini C, Trapassi C, De Benedictis G, Kletsas D, Franceschi C. The G/C915 polymorphism of transforming growth factor beta1 is associated with human longevity: a study in Italian centenarians. Aging Cell. 2004 Dec;3(6):443-8. PubMed PMID: 15569360.

In a study of Italians, this variant observed seen to be less common in centenarians (5.5% allele frequency) vs younger controls (9.5%), p = 0.028. Centenarians: RR: 154, RP: 17, PP: 1. Younger controls: RR: 200, RP: 46, PP: 1.

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het G @ chr19:41858876

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het G @ chr19:41858876

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het G @ chr19:41858876

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het G @ chr19:41858876

 

GS19025 - var-GS19025-1100-36-ASM
het G @ chr19:46550716

 

GS19649 - var-GS19649-1100-36-ASM
het G @ chr19:46550716

 

Other external references
 

    dbSNP
  • rs1800471
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Brucellosis; Cleft Lip; Cleft Palate; Graft vs Host Disease; Hypertension; Periodontitis]
    In conjunction with polymorphism at codon 10, this SNP defines high-, medium- or low-producer haplotype. The Arg allele is associated with higher blood pressure. The C allele is associated with susceptibility to EBV-associated post-transplant lymphoproliferative disorder. The C allele is associated with susceptibility to chronic periodontitis; The G allele may be associated with brucellosis susceptibility. This SNP may play a role in liver graft acceptance. It may be associated with longevity in an Italian population, and it may be associated with clefts of the lip, alveolus and palate.
    www.ncbi.nlm.nih.gov/pubmed/12850397; PubMed ID:15212689; PubMed ID:15569360; PubM
    Web search results (79 hits -- see all)
  • GeneCanvas
    TGFB1 polymorphisms have been described, some of which being associated with bone density. ... mean (SEM) level according to TGFB1/R25P genotype in women of the ...
    genecanvas.idf.inserm.fr/readarticle.php?article_id=39
  • Lack of association between polymorphisms of eight candidate ...
    Still not a subscriber to JACC Imaging or JACC Interventions? ... For TGFB1 R25P and BNP C-1563T, the recessive model was not considered because of the low ...
    content.onlinejacc.org/cgi/content/figsonly/35/1/29
  • PII: S0735-1097(99)00522-7
    R25P and BNP C-1563T, the recessive model was not considered because of the low ... The nonsynonymous TGFB1 R25P poly- morphism, which affects TGFB1 production in vitro (41) ...
    content.onlinejacc.org/cgi/reprint/35/1/29.pdf
  • BioMed Central | Full text | Transforming growth factor beta ...
    Transforming growth factor beta-1 (TGFB1) and peak bone mass: association ... Homozygous knock-out of the TGFB1 gene in mice is associated with an osteopenic ...
    www.biomedcentral.com/1471-2474/6/29
  • Study of candidate genes affecting the progression of renal ...
    ... of these factors except for the R25P (TGFB1) genotype (raw and BH corrected P ... An increase of TGFB1 may cause an overproduction of extracellular matrix leading to fibrosis. ...
    ndt.oxfordjournals.org/cgi/content/full/gfm036v1
  • Genetic modifiers interact with maternal determinants in ...
    ... maternal factors interact to prevent Tgfb1-/- embryonic death due to defective ... been found between carriers of specific TGFB1 and TBR1 polymorphic variants and ...
    hmg.oxfordjournals.org/cgi/content/full/12/13/1579
  • GeneCanvas
    TGFB1/C-509T. TGFB1/C-988A. TGFB1/G-800A. TGFB1/L10P. TGFB1/R25P. TGFB1/T263I. TGFB3/T-24/in4C. TLR4/D299G. TLR4/T399I. TNF/+325/in1 ins/del. TNF/-869ins/del. TNF/C-857T ...
    ecgene.net/.../Polymorphisms/PolymorphismsList.php
  • Combined Genetic Assessment of Transforming Growth Factor ...
    Transforming growth factor-ß1 (TGFB1) is a potent growth suppressor of mammary ... association between either TGFB1*CC and TGFB1*CT genotypes and breast ...
    cancerres.aacrjournals.org/cgi/content/full/65/8/3454
  • Genatlas sheet
    TGFB1-TGFBR1-MAPK signaling in tumor cells promotes tumor angiogenesis (Safina 2007) ... R25P. SNP in the promoter region increasing the risk of chronic obstructive pulmonary ...
    genatlas.medecine.univ-paris5.fr/fiche.php?n=1676
  • Abstract - DGK 2007
    Methods: SNP were screened in: Transforming-growth-factor-beta 1 (TGFb1; L10P, R25P), multi-drug-resistence 1 (MDR1; A893T/S), cytochrome P450 ...
    www.abstractserver.de/dgk2007/ft/abstracts/P566.htm

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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