Association between Polymorphisms and Haplotypes in AKR1B1 and Diabetes Type 2 leading to Complications

Background: A candidate-gene association study in a south eastern Mediterranean population was conducted to investigate the association of five AKR1B1 gene variants (rs2259458 G/T, rs2734653 G/A, rs2670230 C/A, rs1790998 C/A, rs17188118 A/C) with i) diabetes progression and ii) risk of diabetes leading to microvascular complications. Materials and Methods: The cohort consisted of 169 diabetic cases with complications, 107 diseased controls and 315 healthy controls. The disease progression was tested using the generalized odds ratio (ORG). The risk of diabetes leading to complications was tested using the ORs of the additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index. Results: The analysis showed that the five AKR1B1 gene variants are not implicated in disease progression. However, the same AKR1B1 variants are associated with the risk of diabetes leading to complications. Significant results were derived for the additive model of the variant rs2259458 G/T [OR= 1.87 (1.01-3.50)] and the co-dominant model of the variant rs2670230 C/A [OR=1.45 (1.012.04)]. The modes of inheritance for the variants rs2259458 G/T and rs2670230 C/A were “non-dominance” and “dominance of allele A”, respectively. The frequencies of three haplotypes (T-G-A-C-A, G-G-C-C-A and G-A-C-C-A) were significantly different (P≤0.05) between cases and healthy controls. Conclusion: Genetic variation in AKR1B1 gene may alter susceptibility to diabetes leading to complications.