Flavell, D.M.;
Ireland, H.;
Stephens, J.W.;
Hawe, E.;
Acharya, J.;
Mather, H.;
Hurel, S.J.;
(2005)
Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes.
Diabetes
, 54
(2)
pp. 582-586.
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Abstract
Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR) is a master regulator of fatty acid catabolism, and PPAR activators delay the onset of type 2 diabetes. We examined association between three PPAR gene polymorphisms (an AC variant in intron 1, the L162V variant, and the intron 7 GC variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPAR gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 AC (P < 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPAR haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis 45 years) of 3.75 (95% CI 1.65–8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 ± 1.5 and AC + CC 5.3 ± 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes.
| Type: | Article |
|---|---|
| Title: | Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://diabetes.diabetesjournals.org/ |
| Language: | English |
| Additional information: | Copyright © 2005 American Diabetes Association. From Diabetes, vol. 54, 2005; 582-586. Reprinted with permission from The American Diabetes Association. |
| UCL classification: | |
| URI: | https://discovery.ucl.ac.uk/id/eprint/382 |
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