1. The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population
- Author
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Raimund Weitgasser, Franz Krempler, V Mackevics, Thomas K. Felder, Hannes Oberkofler, Bernhard Paulweber, and Wolfgang Patsch
- Subjects
Male ,medicine.medical_specialty ,Genotype ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,Medicine (miscellaneous) ,Single-nucleotide polymorphism ,Type 2 diabetes ,Biology ,Polymorphism, Single Nucleotide ,Body Mass Index ,Insulin resistance ,Risk Factors ,Internal medicine ,Prevalence ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Aged ,education.field_of_study ,Nutrition and Dietetics ,Adiponectin ,Case-control study ,Genetic Variation ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Obesity ,Endocrinology ,Diabetes Mellitus, Type 2 ,Austria ,Case-Control Studies ,Female ,Insulin Resistance ,Sterol Regulatory Element Binding Protein 1 ,Body mass index - Abstract
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). 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. 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. Body mass index (BMI), indices of insulin sensitivity and β-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. 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. 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.
- Published
- 2006