The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort
A. M. Jacobson,
A. D. Paterson,
C. M. Ryan,
P. A. Cleary,
B. H. Waberski,
A. P. Boright
The DCCT/EDIC Research Group
Aims Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting
enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive
dysfunction in the general population, yet little research has examined whether
genetic factors influence risk of cognitive dysfunction in patients with Type
1 diabetes. The long-term follow-up of the Diabetes Control and Complications
Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) population
provides an opportunity to examine if specific genetic variations in APOE and
ACE alter risk for cognitive decline.
Methods Neurocognitive function in Type 1 diabetic subjects from
the DCCT/EDIC study was assessed at DCCT entry and re-assessed approximately 18 years
later, using a comprehensive cognitive test battery. Glycated haemoglobin (HbA 1c )
and the frequency of severe hypoglycaemic events leading to coma or seizures were
measured over the 18-year follow-up. We determined whether the APO ε4 and
ACE intron 16 indel genotypes were associated with baseline cognitive function
and with change over time, and whether they conferred added risk in those subjects
experiencing severe hypoglycaemic events or greater glycaemic exposure.
Results None of the APOE or ACE polymorphisms were associated with either
baseline cognitive performance or change in cognition over the 18-year follow-up.
Moreover, none of the genotype variations altered the risk of cognitive dysfunction
in those subjects with severe hypoglycaemic episodes or high HbA 1c .
Conclusions In this sample of young and middle-aged adults with Type
1 diabetes, APO ε4 and ACE D alleles do not appear to increase risk of cognitive