The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes.
OBJECTIVE
Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship in a large sample of children and adolescents with type 1 diabetes.


METHODS
We studied 585 children and adolescents (mean age 11.9 +/- 4 years, 48.4% males). The frequency of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992-2004. Patients were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR.


RESULTS
In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy-Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61-1.55) relative to II genotype was observed.


CONCLUSIONS
This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents.
Bulsara
M K
MK
School of Population Health, University of Western Australia, 35 Stirling Highway, Crawley, Nedlands, Perth, WA 6009, Australia. max.bulsara@uwa.edu.au
Holman
C D J
CD
van Bockxmeer
F M
FM
Davis
E A
EA
Gallego
P H
PH
Beilby
J P
JP
Palmer
L J
LJ
Choong
C
C
Jones
T W
TW
D000293:Adolescent; D001315:Australia / Q000453:epidemiology; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D007003:Hypoglycemia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012640:Seizures / Q000209:etiology
D007703:Peptidyl-Dipeptidase A