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Disease Markers
Volume 32 (2012), Issue 6, Pages 363-369
http://dx.doi.org/10.3233/DMA-2012-0894

Association of the PGC-1α rs8192678 Variant with Microalbuminuria in Subjects with Type 2 Diabetes Mellitus

Sarah L. Prior,1 Amy R. Clark,1 Danielle A. Jones,1 Steve C. Bain,1 Steve J. Hurel,2 Steve E. Humphries,3 and Jeffrey W. Stephens1

1Diabetes Research Group, Institute of Life Science, Swansea University, Swansea, UK
2Department of Diabetes and Endocrinology, UCL Hospitals, London, UK
3Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, UK

Received 8 March 2012; Accepted 8 March 2012

Copyright © 2012 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.