eprintid: 382
rev_number: 10
eprint_status: archive
userid: 1
dir: disk0/00/00/03/82
datestamp: 2005-03-15 12:00:00
lastmod: 2015-07-23 09:33:08
status_changed: 2008-01-09 13:16:56
type: article
metadata_visibility: show
creators_name: Flavell, D.M.
creators_name: Ireland, H.
creators_name: Stephens, J.W.
creators_name: Hawe, E.
creators_name: Acharya, J.
creators_name: Mather, H.
creators_name: Hurel, S.J.
creators_name: Humphries, S.E.
creators_id: 
creators_id: HIREL86
creators_id: 
creators_id: 
creators_id: 
creators_id: 
creators_id: SJHUR09
creators_id: SEHUM16
title: Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes
ispublished: pub
subjects: 4500
divisions: G3C
note: Copyright © 2005 American Diabetes Association.  From Diabetes, vol. 54, 2005; 582-586. Reprinted with permission from The American Diabetes Association.
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.
date: 2005-02
date_type: published
official_url: http://diabetes.diabetesjournals.org/
vfaculties: VGHCSCI
rae2008: 4
oa_status: green
language: eng
primo: open
primo_central: open_green
lyricists_name: Ireland, H
lyricists_name: Hurel, S
lyricists_name: Humphries, S
lyricists_id: HIREL86
lyricists_id: SJHUR09
lyricists_id: SEHUM16
full_text_status: public
publication: Diabetes
volume: 54
number: 2
pagerange: 582-586
refereed: TRUE
issn: 0012-1797
citation:        Flavell, D.M.;    Ireland, H.;    Stephens, J.W.;    Hawe, E.;    Acharya, J.;    Mather, H.;    Hurel, S.J.;           Flavell, D.M.;  Ireland, H.;  Stephens, J.W.;  Hawe, E.;  Acharya, J.;  Mather, H.;  Hurel, S.J.;  Humphries, S.E.;   - view fewer <#>    (2005)    Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes.                   Diabetes , 54  (2)   pp. 582-586.          Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/382/1/Flavell.pdf