Abstract | AIMS/HYPOTHESIS: SUBJECTS AND METHODS: Two previously well-studied functional APOA4 polymorphisms resulting in the substitution of the amino acid Thr for Ser at codon 347 and Gln for His at codon 360 were genotyped in 634 subjects with type 1 diabetes and 739 non-diabetic control subjects, the participants of the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. RESULTS: The His360 allele was associated with a significantly higher risk of CAC progression among patients with type 1 diabetes (33.7 vs 21.2%, p=0.014), but not in the control subjects (14.1 vs 11.1%, p=0.42). Logistic regression analysis confirmed that the presence of the APOA4 His360 allele predicts an increased risk of progression of coronary atherosclerosis in adults with type 1 diabetes of long duration (odds ratio = 3.3, p=0.003 after adjustment for covariates associated with CAD risk). CONCLUSIONS /INTERPRETATION: This is the first report suggesting an association between the APOA4 Gln360His polymorphism and risk of CAC progression in subjects with type 1 diabetes. Additional studies are needed to explore potential interactions between APOA4 genotypes and metabolic/oxidative stress components of the diabetic milieu leading to rapid progression of atherosclerosis.
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Authors | A Kretowski, J E Hokanson, K McFann, G L Kinney, J K Snell-Bergeon, D M Maahs, R P Wadwa, R H Eckel, L G Ogden, S K Garg, J Li, S Cheng, H A Erlich, M Rewers |
Journal | Diabetologia
(Diabetologia)
Vol. 49
Issue 8
Pg. 1946-54
(Aug 2006)
ISSN: 0012-186X [Print] Germany |
PMID | 16770585
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins A
- apolipoprotein A-IV
- DNA
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Topics |
- Adult
- Amino Acid Substitution
- Apolipoproteins A
(genetics)
- Cohort Studies
- Coronary Artery Disease
(genetics)
- DNA
(blood, genetics, isolation & purification)
- Diabetes Mellitus, Type 1
(genetics)
- Diabetic Angiopathies
(genetics)
- Disease Progression
- Female
- Genotype
- Humans
- Male
- Middle Aged
- Oxidative Stress
- Polymorphism, Genetic
- Reference Values
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