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Context and Objective: Visfatin is a peptide suggested to play a role in glucose homeostasis. In the present study, we investigated the role of genetic variation in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus (T2DM). Design: The visfatin gene (PBEF1) was sequenced in DNA samples from 24 nonrelated Caucasian subjects. Identified genetic variants were used for association analyses of T2DM in a case-control study (503 diabetic subjects and 476 healthy controls) and T2DM-related traits in 626 nondiabetic subjects. The effect of genetic variation in the visfatin gene on its mRNA expression in a subgroup of 157 nondiabetic subjects with measurements of visfatin mRNA expression in visceral and sc fat depots was also analyzed. Results: Seven single-nucleotide polymorphisms (SNPs) and one insertion/deletion were identified. Three SNPs (rs9770242, −948G→T, rs4730153) that were representatives of their linkage disequilibrium groups were genotyped in Caucasians from Germany with a wide range of body fat distribution and insulin sensitivity for association analyses. No association of T2DM with any of the genotyped SNPs or their haplotypes was found. However, the ratio of visceral/sc visfatin mRNA expression was associated with all three genetic polymorphisms (P &amp;lt; 0.05). Moreover, the −948G→T variant was associated with 2-h plasma glucose and fasting insulin concentrations (P &amp;lt; 0.05) in nondiabetic subjects. Conclusions: In conclusion, our data suggest that genetic variation in the visfatin gene may have a minor effect on visceral and sc visfatin mRNA expression profiles but does not play a major role in the development of obesity or T2DM.

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

Genetic Variation in the Visfatin Gene (PBEF1) and Its Relation to Glucose Metabolism and Fat-Depot-Specific Messenger Ribonucleic Acid Expression in Humans