HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM

AbstractType 2 diabetes mellitus (T2DM) is a disease with polygenic inheritance. The expression of major histocompatibility complex class II genes are regulated by several trans-activators. We have studied the expression of HLA-DRB1, RFX, CIITA-P1, PIV transactivators, immunophenotyping of cells, SNPs in CIITA-168 (A/G) and IFN- γ + 874 (T/A) in T2DM patients and controls (n = 201 each). We observed increased frequencies of DRB1*03, DRB1*04 and DRB1*07 and decreased frequencies of DRB1*10, DRB1*14, and DRB1*15 alleles among patients. Significant up-regulations of HLA-DRB1 genes were observed in patients (p <  0.0001). Down-regulated expressions were documented in DRB1*03-homo (p <  0.002) and DRB1*04-homo (p <  0.009) patients. No significant differences were observed for CIITA-P1 expression except DRB1*04-pooled (p <  0.0113). The CIITA-PIV was up-regulated in overall (p <  0.0001), DRB1*03-pooled (p <  0.0006), DRB1*03-hetero (p <  0.0006) and DRB1*03-homo (p <  0.001) T2DM patients. However, significant down-regulations were documented for DRB1*04-pooled (p <  0.040), DRB1*04-hetero (p <  0.060), and DRB1*04-homo (p <  0.027) combinations. Further, significant down-regulations of RFX5 were observed in overall (p <  0.0006), DRB1*04-pooled (p <  0.0022), and DRB1*04-hetero (p <  0.0004) combinations. Immunophenotyping studies revealed significant increase of CD45+ CD14−, CD19+, CD14− and CD8 ce...
Source: Immunogenetics - Category: Genetics & Stem Cells Source Type: research