The -44 C/G (rs1800972) polymorphism of the β-defensin 1 is associated with increased risk of developing type 2 diabetes mellitus.

Background: The aim of this study was to establish the association of two polymorphisms of the β-defensin 1 gene (DEFB1, OMIM#602056) with the risk of developing type 2 diabetes mellitus (T2DM) in a group of Mexican patients.

Methods: The 5'UTR -20 G/A, and -44 C/G polymorphisms of DEFB1 gene were genotyped by 5' exonuclease TaqMan assays in a group of 252 patients with T2DM and 522 healthy control.

Results: Under dominant and additive models adjusted for the risk factors, the C allele of the -44 C/G polymorphism was associated with increased risk of T2DM (OR = 1.63, 95% CI = 1.07-2.48, pC  = 0.021 and OR = 1.42, 95% CI = 1.05-1.91, pC  = 0.023, respectively). In addition, the linkage disequilibrium analysis showed that AC haplotype was associated with an increased risk of developing T2DM (OR = 4.39, p = 0.04). The in-silico analysis showed that the -44 C allele produces a binding site for the transcription factor Ikaros (IK).

Conclusion: This study demonstrates that the C allele of -44 C/G polymorphism, as well as haplotype AC are associated with the presence of T2DM in the Mexican population. The variation in this polymorphism of the DEFB1 gene could increase the migration of the macrophages to pancreatic islets accelerate the β-cell dysfunction in T2DM.