Affiliations: Diabetes Research Group, Institute of Life Science,
Swansea University, Swansea, UK | Department of Diabetes and Endocrinology, UCL
Hospitals, London, UK | Centre for Cardiovascular Genetics, British Heart
Foundation Laboratories, Royal Free and University College London Medical
School, London, UK
Note: [] Corresponding author: Dr. Sarah Prior, Diabetes Research Group,
3rd Floor, Institute of Life Sciences, Swansea University, Swansea, SA2 8PP,
UK. Tel.: +44 0 1792 295073; Fax: +44 0 1792 602147; E-mail:
s.l.prior@swansea.ac.uk
Abstract: PPAR-γ co-activator-1α (PGC-1α) is a
tissue-specific transcriptional co-activator involved in the regulation of
antioxidant enzymes. The A-allele of the rs8192678 PGC-1 α} (G>A) gene
variant has previously been associated with nephropathy in Korean and
Indian-Asian type 2 diabetes mellitus (T2DM) samples. Our aim was to examine
the association between this variant and urine albumin exccretion in European
subjects with T2DM. Genotyping was performed on 583 European subjects with T2DM and
examined in relation to urinary albumin, plasma oxidized-LDL and small
dense-LDL percentage. We observed a significant association between genotype
(GG/GA/AA) and urinary albumin (normoalbuminuria v micro/macroalbuminuria:
48.6/39.7/11.7% v 38.2/51.2/10.5%, p=0.02; for GG v GA/AA, p=0.01). The odds
ratio for micro/macroalbuminuria in GA and AA subjects relative to GG were 1.70
[1.15–2.50], p=0.008 and 1.20 [0.66–2.16], p=0.56 respectively (for
GA/AA v GG: 1.58 [95% CI: 1.09–2.27], p=0.02). There was a significant
association between the A allele and a higher percentage of small dense-LDL
particles (GG v GA v AA: 70.8 [58.01–81.06] % v 72.8 [56.18–81.19]
% v 78.9 [67.16–85.33] %, p=0.03). In European subjects with T2DM the GA relative to the GG genotype is
associated with a 70% increase in the risk of micro/microalbuminuria.
Furthermore, homozygosity for the A-allele is also associated with a
preponderance of small dense-LDL particles.
Keywords: PGC-1α, type 2 diabetes mellitus, microalbuminuria, oxidative stress
