RGD Reference Report - Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes. - Rat Genome Database

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Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes.

Authors: Pedersen-Bjergaard, U  Dhamrait, SS  Sethi, AA  Frandsen, E  Nordestgaard, BG  Montgomery, HE  Pramming, S  Hougaard, P  Thorsteinsson, B 
Citation: Pedersen-Bjergaard U, etal., Am J Med. 2008 Mar;121(3):246.e1-8.
RGD ID: 2313551
Pubmed: PMID:18328310   (View Abstract at PubMed)
DOI: DOI:10.1016/j.amjmed.2007.12.002   (Journal Full-text)

BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma angiotensinogen concentration and serum ACE activity. RESULTS: Three risk factors for severe hypoglycemia were identified: plasma angiotensinogen concentration in the upper quartile (relative rate [RR] vs. lower quartile 3.1, 95% confidence interval [CI,] 1.4-6.8), serum ACE activity in the upper quartile (RR vs. lower quartile 2.9, 95% CI, 1.3-6.2), and homo- or hemizygosity for the A-allele of the X chromosome-located AT2R 1675G/A polymorphism (RR vs. noncarriers 2.5, 95% CI, 1.4-5.0). The three risk factors contributed independently to prediction of severe hypoglycemia. A backward multiple regression analysis identified a high number of renin-angiotensin system-related risk factors and reduced ability to perceive hypoglycemic warning symptoms (impaired hypoglycemia awareness) as predictors of severe hypoglycemia. CONCLUSIONS: High renin-angiotensin system activity and the A-allele of the AT2R 1675G/A polymorphism associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypoglycemia  IAGP 2313551associated with Diabetes Mellitus more ...RGD 
hypoglycemia  ISOAGTR2 (Homo sapiens)2313551; 2313551associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agtr2  (angiotensin II receptor, type 2)

Genes (Mus musculus)
Agtr2  (angiotensin II receptor, type 2)

Genes (Homo sapiens)
AGTR2  (angiotensin II receptor type 2)


Additional Information