PMID- 24333266
OWN - NLM
STAT- MEDLINE
DCOM- 20140304
LR  - 20171116
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 536
IP  - 1
DP  - 2014 Feb 15
TI  - Epigenetic modulation of RFC1, MHC2TA and HLA-DR in systemic lupus erythematosus: 
      association with serological markers and six functional polymorphisms of 
      one-carbon metabolic pathway.
PG  - 45-52
LID - S0378-1119(13)01620-X [pii]
LID - 10.1016/j.gene.2013.11.094 [doi]
AB  - The current study was conducted to elucidate the effect of genetic variations in 
      one-carbon metabolism on the epigenetic regulation of major histocompatibility 
      complex II transactivator (MHC2TA), reduced folate carrier 1 (RFC1/SLC19A1) and 
      human leukocyte antigen (HLA)-DR in systemic lupus erythematosus (SLE). 
      PCR-RFLP/AFLP, bisulfite-sequencing and real-time PCR approaches were used for 
      genetic, epigenetic and expression analysis respectively. SLE cases exhibited 
      elevated plasma homocysteine levels compared to healthy controls (24.93 +/- 1.3 vs. 
      11.67 +/- 0.48 mumol/l), while plasma folate levels showed no association (7.10 +/- 
      2.49 vs. 7.64 +/- 2.09 ng/ml). The RFC1 80G>A polymorphism showed 1.32-fold risk 
      (95% CI: 1.02-1.72) for SLE, while glutamate carboxypeptidase II (GCPII) 1561C>T 
      showed reduced risk (OR: 0.47, 95% CI: 0.24-0.90). The expression of RFC1 (0.37 +/- 
      0.09 vs. 0.60 +/- 0.17) and HLA-DR (0.68 +/- 0.17 vs. 0.98 +/- 0.02) was down regulated 
      in the SLE cases. The hypermethylation of RFC1 as observed in the current study 
      may contribute for its down regulation. Plasma folate and thymidylate synthase 
      (TYMS) 5'-UTR 28 bp tandem repeat showed an inverse association with methylation 
      of RFC1 and MHC2TA. SLE cases with hypocomplementemia showed hypermethylation of 
      RFC1, hypomethylation/up regulation of MHC2TA and down regulation of HLA-DR. The 
      hypermethylation of MHC2TA and down regulation of RFC1, MHC2TA and HLA-DR were 
      observed in anti-cardiolipin antibody positive SLE cases. The up regulation of 
      RFC1 and HLA-DR was observed in anti-dsDNA antibody positive SLE cases. The 
      hypomethylation/upregulation of RFC1 and MHC2TA was observed in anti-RNP antibody 
      positive cases. To conclude, one-carbon genetic variants influence epigenetic of 
      MHC2TA and RFC1, thus contributing to phenotypic heterogeneity of SLE.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Rupasree, Yedluri
AU  - Rupasree Y
AD  - Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical 
      Sciences (NIMS), Hyderabad 500082, India.
FAU - Naushad, Shaik Mohammad
AU  - Naushad SM
AD  - School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, 
      Thanjavur 613401, India.
FAU - Rajasekhar, Liza
AU  - Rajasekhar L
AD  - Department of Rheumatology, Nizam's Institute of Medical Sciences (NIMS), 
      Hyderabad 500082, India.
FAU - Kutala, Vijay Kumar
AU  - Kutala VK
AD  - Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical 
      Sciences (NIMS), Hyderabad 500082, India. Electronic address: 
      vijaykutala@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131212
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Biomarkers)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RFC1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 7440-44-0 (Carbon)
RN  - EC 3.6.4.- (Replication Protein C)
SB  - IM
MH  - Biomarkers/blood
MH  - Carbon/metabolism
MH  - Case-Control Studies
MH  - Epigenesis, Genetic/*physiology
MH  - Female
MH  - Genetic Association Studies
MH  - HLA-DR Antigens/*genetics
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*blood/epidemiology/*genetics
MH  - Male
MH  - Metabolic Networks and Pathways/genetics
MH  - Nuclear Proteins/*genetics
MH  - Polymorphism, Genetic
MH  - Replication Protein C/*genetics
MH  - Trans-Activators/*genetics
OTO - NOTNLM
OT  - CI
OT  - DNA methylation
OT  - GCPII
OT  - HLA
OT  - HWE
OT  - Hardy-Weinberg equilibrium
OT  - MHC class II transactivator
OT  - MHC2TA
OT  - MTHFR
OT  - MTR
OT  - OR
OT  - One-carbon metabolism
OT  - RFC1
OT  - Reduced folate carrier 1
OT  - SLE
OT  - Systemic lupus erythematosus
OT  - TYMS
OT  - confidence interval
OT  - glutamate carboxypeptidase II
OT  - human leukocyte antigen
OT  - major histocompatibility complex II transactivator
OT  - methionine synthase
OT  - methylene tetrahydrofolate reductase
OT  - odds ratio
OT  - reduced folate carrier 1
OT  - systemic lupus erythematosus
OT  - thymidylate synthase
EDAT- 2013/12/18 06:00
MHDA- 2014/03/05 06:00
CRDT- 2013/12/17 06:00
PHST- 2013/11/06 00:00 [received]
PHST- 2013/11/30 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/03/05 06:00 [medline]
AID - S0378-1119(13)01620-X [pii]
AID - 10.1016/j.gene.2013.11.094 [doi]
PST - ppublish
SO  - Gene. 2014 Feb 15;536(1):45-52. doi: 10.1016/j.gene.2013.11.094. Epub 2013 Dec 
      12.