The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population
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Date
2007-07-10
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Abstract
Context: The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). Objective: We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. Design, settings and participants: We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. Main outcome measures: Body mass index (BMI), indices of insulin sensitivity and β-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. Results: Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. Conclusions: We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.
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Funding Information: This study was supported by grants from the Oesterrei-chische Nationalbank (Project No. 10678 and 10932), the Medizinische Forschungsgesellschaft Salzburg and a grant from the Land Salzburg. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.
Keywords
Adiponectin, Single nucleotide polymorphism, SREBP-1c, Type 2 diabetes, 3.1 Basic medicine, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Medicine (miscellaneous), Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics, SDG 3 - Good Health and Well-being
Citation
Felder, T K, Oberkofler, H, Weitgasser, R, Mackevics, V, Krempler, F, Paulweber, B & Patsch, W 2007, 'The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population', International Journal of Obesity, vol. 31, no. 7, pp. 1099-1103. https://doi.org/10.1038/sj.ijo.0803505