GEPHE SUMMARY
GepheID
GP00000084
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Homo sapiens
Trait State in Taxon B
Homo sapiens
Ancestral State
Data not curated
Taxonomic Status
Taxon A
Latin Name
Common Name
human
Synonyms
human; man; Homo sapiens Linnaeus, 1758; Home sapiens; Homo sampiens; Homo sapeins; Homo sapian; Homo sapians; Homo sapien; Homo sapience; Homo sapiense; Homo sapients; Homo sapines; Homo spaiens; Homo spiens; Humo sapiens
Rank
species
Lineage
Show more ... opterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini; Hominoidea; Hominidae; Homininae; Homo
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
human
Synonyms
human; man; Homo sapiens Linnaeus, 1758; Home sapiens; Homo sampiens; Homo sapeins; Homo sapian; Homo sapians; Homo sapien; Homo sapience; Homo sapiense; Homo sapients; Homo sapines; Homo spaiens; Homo spiens; Humo sapiens
Rank
species
Lineage
Show more ... opterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini; Hominoidea; Hominidae; Homininae; Homo
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
AMPD1
Synonyms
MAD; MADA; MMDD
Sequence Similarities
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
GO - Cellular Component
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
Molecular Type
Aberration Type
Molecular Details of the Mutation
unknown
Experimental Evidence
Authors
Wessels JA; van der Kooij SM; le Cessie S; Kievit W; Barerra P; Allaart CF; Huizinga TW; Guchelaar HJ; et al. ... show more
Abstract
To develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA).

Two hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS < or = 2.4 at 6 months) and nonresponders. In case of differences, a stepwise selection procedure identified the predictors for response. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of patients.

The model for MTX efficacy consisted of sex, rheumatoid factor and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and MTHFD1 genes. This prediction model was transformed into a scoring system ranging from 0 to 11.5. Scores of < or = 3.5 had a true positive response rate of 95%. Scores of > or = 6 had a true negative response rate of 86%. Sixty percent of the patients were categorized as either responders or nonresponders, whereas 32% of the patients were categorized using a nongenetic model. Evaluation of the model in 38 additional patients with RA supported the results.

This study established a model for predicting the efficacy of MTX in patients with RA. This pharmacogenetic model may lead to better-tailored initial treatment decisions in patients with RA.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
No matches found.
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