PMID- 33754173
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 1432-1211 (Electronic)
IS  - 0093-7711 (Linking)
VI  - 73
IP  - 4
DP  - 2021 Aug
TI  - HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the 
      susceptibility to T2DM.
PG  - 291-305
LID - 10.1007/s00251-021-01212-x [doi]
AB  - Type 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-gamma + 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 cells and elevated level of expression of IFN-gamma (p < 0.0001) in patients. A 
      significant increase of TT (p < 3.35 x 10(-6)) and decrease of TA 
      (p < 4.57 x 10(-4)) genotypes of IFN-gamma + 874 (T/A) and an increase of GG 
      (p < 0.001) and decrease of AG (p < 8.24 x 10(-5)) genotypes of CIITA-168 A/G 
      SNPs were observed. The combinatorial analysis revealed susceptible associations 
      for DRB1*03 + AA, *03 + AG, *03 + GG and *04 + GG and protective associations for 
      DRB1*10 + AG, *10 + GG, *15 + AG, and *14 + GG combinations. Thus, the present 
      study corroborated the effect of differential expressions of promoters of risk 
      alleles in the pathogenesis of T2DM.
FAU - Chinniah, Rathika
AU  - Chinniah R
AD  - Department of Immunology, School of Biological Sciences, Madurai, Tamil Nadu, 
      625021, India.
FAU - Sevak, Vandit
AU  - Sevak V
AD  - Department of Immunology, School of Biological Sciences, Madurai, Tamil Nadu, 
      625021, India.
FAU - Pandi, Sasiharan
AU  - Pandi S
AD  - Department of Immunology, School of Biological Sciences, Madurai, Tamil Nadu, 
      625021, India.
FAU - Ravi, Padma Malini
AU  - Ravi PM
AD  - Department of Immunology, School of Biological Sciences, Madurai, Tamil Nadu, 
      625021, India.
FAU - Vijayan, Murali
AU  - Vijayan M
AD  - Department of Internal Medicine, Texas Tech University Health Sciences Center, 
      Lubbock, TX, 79430, USA.
FAU - Kannan, Arun
AU  - Kannan A
AD  - The Madurai Institute of Diabetes and Endocrine Practice Research, Madurai, Tamil 
      Nadu, 625 001, India.
FAU - Karuppiah, Balakrishnan
AU  - Karuppiah B
AD  - Department of Immunology, School of Biological Sciences, Madurai, Tamil Nadu, 
      625021, India. immunobala@mkuniversity.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210322
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/epidemiology/genetics/*pathology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nuclear Proteins/genetics/*metabolism
MH  - *Polymorphism, Single Nucleotide
MH  - Trans-Activators/genetics/*metabolism
OTO - NOTNLM
OT  - CIITA
OT  - HLA
OT  - MHC
OT  - Promoter
OT  - RFX5
OT  - T2DM
EDAT- 2021/03/24 06:00
MHDA- 2021/10/05 06:00
CRDT- 2021/03/23 06:59
PHST- 2020/12/03 00:00 [received]
PHST- 2021/03/01 00:00 [accepted]
PHST- 2021/03/24 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/03/23 06:59 [entrez]
AID - 10.1007/s00251-021-01212-x [pii]
AID - 10.1007/s00251-021-01212-x [doi]
PST - ppublish
SO  - Immunogenetics. 2021 Aug;73(4):291-305. doi: 10.1007/s00251-021-01212-x. Epub 
      2021 Mar 22.