@article{discovery382,
         journal = {Diabetes},
           title = {Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes},
           pages = {582--586},
            note = {Copyright {\copyright} 2005 American Diabetes Association.  From Diabetes, vol. 54, 2005; 582-586. Reprinted with permission from The American Diabetes Association.},
            year = {2005},
          number = {2},
          volume = {54},
           month = {February},
            issn = {0012-1797},
             url = {http://diabetes.diabetesjournals.org/},
        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 {\ensuremath{<}} 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P {\ensuremath{<}} 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 {$\pm$} 1.5 and AC + CC 5.3 {$\pm$} 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes.},
          author = {Flavell, D. M. and Ireland, H. and Stephens, J. W. and Hawe, E. and Acharya, J. and Mather, H. and Hurel, S. J. and Humphries, S. E.}
}