Expression of JAZF1, ABCC8, KCNJ11and Notch2 genes and vitamin D receptor polymorphisms in type 2 diabetes, and their association with microvascular complications.

BACKGROUND

We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients.

METHODS

The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique.

RESULTS

After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases ( = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only ( = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups ( = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls ( = 0.001), while no difference was detected between complicated and noncomplicated cases ( = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions ( = 0.7 and 0.1, respectively) and allele frequencies ( = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele ( = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications ( = 0.02 and 0.003, respectively).

CONCLUSION

Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.