Characterization of the annexin I gene and evaluation of its role in type 2 diabetes

In a previous study, we identified suggestive linkage between type 2 diabet es and a locus on chromosome 9p13-q21. This region contains the gene annexi n I (ANXA1), encoding a protein suggested to be involved in both insulin se cretion and insulin action. In this study, we sequenced the exon/intron bou ndaries of the human ANXA1 gene and performed mutation screening in 41 indi viduals from the initial linkage study. We identified five single nucleotid e polymorphisms A58G, A401G, intronic variance sequence (IVS)8-28A/G, IVS11 +31A/G, and IVS12-11T/G, which were further tested for association to diab etes in 197 parent/offspring trios using the transmission disequilibrium. t est. No significant association with type 2 diabetes was observed, although the common A allele of the +58A/G variant gave a 22:12 transmission distor tion (P = 0.12). This variant was further genotyped in 481 case and control subjects, but no difference in allele, genotype, or haplotype frequencies were observed between the groups. Further, a novel polymorphic (CA)(15-25), repeat in intron 11 was genotyped in the subjects included in the initial linkage study. No improvement of the original finding was observed. We ther efore concluded that the ANXA1 gene is unlikely to harbor variants that con tribute to risk of type 2 diabetes.