The ENPP1 K121Q polymorphism modulates developing of bone disorders in type 2 diabetes: A cross sectional study

Osteoporosis and osteopenia are common diseases in every population. Type 2 diabetes mellitus (T2DM) can lead to the development of various complications, such as bone disorders especially among elderly individuals. Studies suggested that ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1) is contributed in insulin resistance and also the inhibition of bone mineralization. In this study, association of K121Q (rs1044498) polymorphism of the ENPP1 gene with T2DM and bone disorders is evaluated.

Four-hundred-and-ninety females who were classified based on bone mineral density (BMD) at lumbar spine and femur were included in this study. In addition, participants were classified according to their diabetes status. K121Q polymorphism was evaluated by the PCR-PFLF technique. One-way ANOVA was used for comparison of various analyzed factors in diseases subgroups and K121Q genotypes. Association of K121Q polymorphism with diabetes and bone disorders was evaluated by logistic regression.

Significant association was observed between K121Q polymorphism with osteoporosis and osteopenia (p=0.041, p=0.029, respectively), but a similar pattern was not observed in T2DM status (p=0.723). Moreover, in diabetic patients, K121Q polymorphism showed a better prediction potential for the development of bone disorders in comparison to non-diabetic subjects (p=0.018; OR=4.63, p=0.540; OR=1.31). There were no significant differences between K121Q genotypes with FBS, Ca, P, vitamin D, PTH and BMD status.

The present study implies that K121Q polymorphism of ENPP1 gene is able to modulate the development of bone disorders in T2DM. Therefore in diabetic patients screening of this polymorphism is suggested for the monitoring of these persons.