Peroxisome proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes
Flavell, DM; Ireland, H; Stephens, JW; Hawe, E; Acharya, J; Mather, H; Hurel, SJ; Humphries, SE
HERO ID
735851
Reference Type
Journal Article
Year
2005
Language
English
PMID
| HERO ID | 735851 |
|---|---|
| In Press | No |
| Year | 2005 |
| Title | Peroxisome proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes |
| Authors | Flavell, DM; Ireland, H; Stephens, JW; Hawe, E; Acharya, J; Mather, H; Hurel, SJ; Humphries, SE |
| Journal | Diabetes |
| Volume | 54 |
| Issue | 2 |
| Page Numbers | 582-586 |
| Abstract | Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)alpha is a master regulator of fatty acid catabolism, and PPARalpha activators delay the onset of type 2 diabetes. We examined association between three PPARalpha gene polymorphisms (an A-->C variant in intron 1, the L162V variant, and the intron 7 G-->C variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPARalpha gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 A-->C (P < 0.001) and intron 7 G-->C (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPARalpha 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 PPARalpha gene variation influences the onset and progression of type 2 diabetes. |
| Pmid | 15677519 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |