The rs45454496 (E1813K) variant in the adiposity gene ANK2 doesn't associate with obesity in Southern European subjects

Recently ANK2, encoding ankyrin-B (AnkB), has been proposed as an obesity susceptibility gene. AnKB negatively regulates the expression of glucose transporter 4 (GLUT4) in adipocytes, and it has been hypothesized that functional alterations of AnkB may determine the persistence of GLUT4 on the cell surface, increasing glucose transport in adipocytes. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet. AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4. Functional alterations have been observed in ANK2 gene in European Americans and African Americans and have been proposed as candidates to contribute to obesity susceptibility in humans. Considering that variants of ANK2 gene were previously observed in subjects of American and African American ethnicity, and that these variants were never studied in association with obesity, we performed a genetic association analysis with obesity in a cohort of Southern European subjects. For this study 1900 Italian subjects with body mass index (BMI) between 16 and 91 were selected. All subjects underwent clinical examination, anthropometric measurements and routine laboratory tests. The SNPs rs45454496 (E1813K) and rs35530544 (L1622I) have been studied in DNAs by Eco TM Real-Time PCR System by Illumina. Among the 1900 subjects we identified 15 (frequency 0.7%) heterozygous subjects for the rs45454496 variant and no homozygous subject. The observed frequency in our population is more than double that observed in other populations of European origin (0.7% vs 0.3%, p = 0.3). We then analysed the association between this polymorphism and clinical and biochemical characteristics. Carriers of the mutation showed no significantly differences compared to wild-type subjects in any of the parameters examined. Population stratification by BMI showed a random distribution of the rs45454496 variant according to weight. Also, population stratification based on glycaemic alterations showed no association of the rs45454496 variant with categories of glucose metabolism. Finally, we analysed the study cohort for the rs35530544, but we did not observe any subject carrying the variant in an initial sample of 840 patients. In conclusion, we observed that the rs45454496 (E1813K) variant of ANK2 gene, although showing a higher frequency in our Southern European population (0.7%) than the frequencies reported in other populations of European origin, in the analysed sample does not seem to have effects on clinical and metabolic alterations.