alexa Emerging Vitamin D Receptor-Centered Patterns of Genetic Overlap across Some Autoimmune Diseases and Associated Cancers | OMICS International
ISSN: 2157-7412
Journal of Genetic Syndromes & Gene Therapy

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Emerging Vitamin D Receptor-Centered Patterns of Genetic Overlap across Some Autoimmune Diseases and Associated Cancers

Yue Zhang*

Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada

*Corresponding Author:
Yue Zhang
CRCHUM, Notre-Dame Hospital, 1560 Sherbrooke Street East
Pavillon DeSève, Room Y2625, Montreal, Quebec, Canada H2L 4M1
Tel: 1-514-890-8000(ext 23875)
Fax: 1-514-412-7583
E-mail: [email protected]

Received date: December 11, 2013; Accepted date:December 15, 2013; Published date: December 22, 2013

Citation: Zhang Y (2013) Emerging Vitamin D Receptor-Centered Patterns of Genetic Overlap across Some Autoimmune Diseases and Associated Cancers. J Genet Syndr Gene Ther 4:e123. doi:10.4172/2157-7412.1000e123

Copyright: © 2013 Zhang Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Genetic Syndromes & Gene Therapy

Genetic Regulatory Network (GRN) of Vitamin D Receptor-Centered Hypothesis

An increased risk for complex diseases such as Autoimmune Diseases (ADs) and/or cancer is associated with the aging process but we are not sure what causes such outcomes. With comparative advantages of different model system and recent Genome-Wide Association Studies (GWAS), and ChIP-seq/ChIP-chip studies, we distilled out one attention-deserved Vitamin D receptor –centered hypothesis: the genetic regulatory network of vitamin D receptor (VDR, homologue of DAF-12 in Caenorhabditiselegans) may play a central role as a common basis preventing some autoimmune diseases and associated cancers [1-3]. Further, we predict, similar to DAF- 21 /HSP90VDR may buffer disease-causing genetic mutations and/ or variations the diseases phenotype may come up with polygenic genetic mutations and/or variations along with deficiency of vitamin D and lacking of UVB and mal-functional DAF-12/VDR with lose of its buffering ability as a capacitor [1,3,4]. Decoding the genetics of these complex diseases associated with the aging process is helpful to understand the controversies the beneficial effects of vitamin D supplementation on them [5]. We highlighted that environmental factor-induced mal-functional DAF-12/VDR may be postulated to cause in situ dys-regulation of expression of an array of its target genes (in press, whose citrullination of such in situ dys-regulated genes might be tightly mediated by VDR-orchestrated processes and consequently ends with autoimmunity. If it were the case, those “loci” identified by GWAS collectively have a significance of gene function [1,6].

GRN of VDR (and DAF-12) may Act as a Capacitor

We human beings survive well the challenges of genetic variations and environmental factors via the robustness of complex genetic regulatory networks in our bodies, possibly including one of VDR as a capacitor and probably similar to DAF-12 in C.elegans [7]. Decreases in the VDR pathway resulting from of vitamin D deficiency and/or a lack of UVB could enhance some disease-causing morphological variants. Moreover, GRN of DAF-12/VDR intertwines microRNA regulations, autophagy, longevity and cellular reprogramming, and forward or feedback loops [4]. When VDR function is in studys-regulated due to genetic defects or by vitamin D unavailability, it may remodel many different processes alongside adjustments of multiple signal transducers and thereby simultaneously disturbing several developmental pathways as DAF-12/VDR if out of its buffering capability, the ADs and associated cancers may come to the patients [1,8].

GRN of VDR may be Consider as Common Basis for ADs and Associated Cancers?

Although further testing is awaiting for, one GWAS reveals that one allelic VDR variant may link to clinical autoimmune antibodies including anti-p150 (TRIM33/ TIF-1γ)/p140(TRIM24/TIF-1α) whose natural self-antigens may correlate with protein products encoded by TIF-1γ/α, whose homologues flt-1 and nhl-2 are direct targets of DAF-12/VDR [8,9]. DAF-12/VDR target genes from our ChIP-chip screening showed many overlaps with validated homologues identified in human VDR studies and significantly enriched near genes that are pathologically associated with ADs and cancer [8]. But it is necessary to experimentally test these overlaps in human VDR.

One of our recent experiences is as follow

Once new key regulators for ADs were published online first, we predicted, they would act as putative target candidates of DAF- 12/VDR; amazingly, the majority if not all turned out to be the case. For instance, key regulator FBN1 responsible for fibrosis and autoimmunity in mouse models of scleroderma is found as the homolog of fbl-1 in C. elegans, the putative target of DAF-12/VDR [10]. Another GWAS identified genetic variants for joint damage progression in autoantibody-positive rheumatoid arthritis (RA) and three key genes (sperm-associated antigen 16 (SPAG16), and Matrix Metallopeptidase1 and 3 (MMP1 and MMP3) [11]. They are among human homologue candidates of DAF-12/vitamin D receptor (VDR) target genes [2,7,8,12]. However, Miller et al. reporting on GWAS of Dermatomyositis (DM), found a genetic overlap with other ADs, as the first genetic predispositions towards ADs shared with DM [13]. The latest case is rpc-1 responsible for both the scleroderma and cancer [14]. Moreover, other patterns of genetic overlap across ADs have emerged [13,15]. Likely, a malfunction of VDR could affect the pathogenesis of RA and associated cancers expanding to many other ADs, Paraneoplastic Neurological Diseases(PND) and DM (Table 1) [1,13,14,16,17-24]. In addition, VDR ChIP-seq in primary CD4+ cells relates serum 25-hydroxyvitamin D levels to autoimmune disease [25]. In closing, the patho-physiology of ADs (at least subgroup) may share their common underlying mechanisms of genetic regulatory network of VDR.


Before a definitive rejection or acceptance of the hypothesis can be made, further studies are warranted including first confirmation of VDR in mammalian systems. If being accepted, much attention will need pay to preventive effects of vitamin D, particularly if some processes under the control of VDR are irreversible like “one-way” traffic. However, without a thorough understanding of the mechanisms of ADs and associated cancers, it seems to be too early to claim that the majority of Americans and Canadians are receiving adequate amounts of both calcium and vitamin D, though it is necessary to warn of the toxicity of vitamin D with bigger doses for some populations [26,27]. Studies should also classify the different degrees of “at-risk” genotype (Zhang Y, in press) in that the vitamin D deficiency likely remains under recognised, undetermined and untreated. As we human beings are out-breeding, the models may be extremely useful in eventually contributing to an understanding of the effects of vitamin D and its receptors at complex diseases such as ADs and associated cancers at both cellular and organism levels [6,16].

Aceview mapping of homologues of the DAF-12/VDRtarget genes to key genes described in recent AD or associated cancer-related publications
Gene (Human homologue of the VDR target/C.eleganshomologue of the DAF-12 target) Type of diseases References
ZGPAT/C33H5.17 UC,CD [21]
CCR7 /R106.2 T1D [21]
PLCL/pll-1 CD,DM [13,21]
RPL19PB/rpl19 MS [21]
TNFAIP3/Y59C1A.1 RA, SLE, UC, SSc [21]
Pxk/ wnk-1 SLE [21]
IKZF1/PRDM16/egl-43,the closest DAF-12/VDR binding loci 15 kb distant from the R53.5, R53.6, R53.7a, R53.8 regions. CD [21]
BLK/src-1  SLE,RA,DM [13, 21]
RBPj/lag-1    T1D, RA [21]
GOT1/T01C8.5 CD, UC [21]
Jak2/csnk-1/Y106G6E.6 CD, UC [21]
IFIH1/drh-1 Multiple [21]
Jak2/ csnk-1 CD, UC [23]
NKX2.3/ceh-24. CD,UC [23]
SMAD3/daf-3.   [23]
PRDM1/blmp-1, the closest DAF-12/VDR binding locus in ChIP-chip online target list <10 kb distant from the Y106G6H.1 region. CD,UC [23]
HNF4a/nhr-64. UC [23]
LAMB1/lam-1/W03F8.5. UC [23]
xpa-1 /K07G5.2,  the closest DAF-12/VDR binding locus in the ChIP-chip online target list to the K07G5.1 and K07G5.6 regions. PND [17]
Smarcal1/C16A3.1, the closest DAF-12/VDR binding locus in the ChIP-chip online target list to the C16A3.6, C16A3.7a, C16A3.8and C16A3.11 regions. PND [17]
ELF1/elf-1. PND [17]
DBR1/C55B7.8 the closest DAF-12/VDR binding locus in the ChIP-chip online target list 5 kb distant from the C55B7.3 region. PND [17]
TIFα/TRIM24/flt-1 DM, cancer [18,27]
TIFβ/TRIM28/ncl-1 DM, cancer [18]
TIFγ/TRIM33/nhl-2 DM, cancer [18]
AIRE/Mi-2β/let-418 DM, cancer [22,24]
Foxp3/fkh-7 DM, cancer [22,24]
ADAM33/adm-2 Asthma [22]
GPRA/gnrr-1/F5D7.3 Asthma [22]
RPC-1/rpc-1 SSC, cancer [14]
Topoisomerase I /top1 SSC [14]

Table 1: Representative DAF-12 and VDR -shared/conserved target genes and the type of associated AD and cancers.


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 5th International Conference on Human Genetics and Genetic Disorders September 21-22,2018 Philadelphia, USA Theme: Sharing Discoveries of the Future Human Genome
    September 21-22,2018 Philadelphia, USA

Article Usage

  • Total views: 12053
  • [From(publication date):
    December-2013 - Jul 22, 2018]
  • Breakdown by view type
  • HTML page views : 8259
  • PDF downloads : 3794

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals


[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7