RGD Reference Report - Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta2 agonist and steroid response. - Rat Genome Database

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Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta2 agonist and steroid response.

Authors: Vonk, JM  Postma, DS  Maarsingh, H  Bruinenberg, M  Koppelman, GH  Meurs, H 
Citation: Vonk JM, etal., Pharmacogenet Genomics. 2010 Mar;20(3):179-86.
RGD ID: 5129205
Pubmed: PMID:20124949   (View Abstract at PubMed)
DOI: DOI:10.1097/FPC.0b013e328336c7fd   (Journal Full-text)

RATIONALE: Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta2 agonists. OBJECTIVES: We investigated the association between arginase 1 and arginase 2 polymorphisms and adult asthma, asthma severity and treatment response in a longitudinal cohort of 200 asthma patients. METHODS: Patients were studied during 1962-1975 and reexamined during 1990-1999, together with their families. Longitudinal data on lung function and treatment were extracted from medical records. Associations between haplotype-tagging polymorphisms in arginase 1 (n=3) and arginase 2 (n=8) and asthma, asthma severity, acute response to bronchodilators and chronic response to inhaled corticosteroids were analyzed. MEASUREMENTS AND MAIN RESULTS: Two polymorphisms in arginase 2 (rs17249437 and rs3742879) were associated with asthma and with more severe airway obstruction. Increased airway hyperresponsiveness and lower beta2 agonist reversibility, but not anticholinergic reversibility, were associated with both arginase 1 and arginase 2. Inhaled corticosteroids slowed down the annual FEV1 decline, which was significantly less effective in homozygote carriers of the C-allele of the arginase 1 polymorphism, rs2781667. CONCLUSION: We show that previously reported associations between arginase polymorphisms and childhood asthma are also present in adult asthma and the previously found associations with lower reversibility are specific for beta2 agonists. Furthermore, we identified associations of arginase 1 and arginase 2 genes with asthma severity, as reflected by a lower lung function, more severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. Studies on the functionality of the polymorphisms are warranted to further unravel the complex mechanisms underlying these observations.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IAGP 5129205DNA:SNP: :rs2781667 (human)RGD 
asthma severityIAGP 5129205DNA:SNP: :rs3742879 and rs17249437 (human)RGD 
asthma  ISOARG1 (Homo sapiens)5129205; 5129205DNA:SNP: :rs2781667 (human)RGD 
asthma severityISOARG2 (Homo sapiens)5129205; 5129205DNA:SNP: :rs3742879 and rs17249437 (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arg1  (arginase 1)
Arg2  (arginase 2)

Genes (Mus musculus)
Arg1  (arginase, liver)
Arg2  (arginase type II)

Genes (Homo sapiens)
ARG1  (arginase 1)
ARG2  (arginase 2)


Additional Information