PMID- 20596022
OWN - NLM
STAT- MEDLINE
DCOM- 20100806
LR  - 20220408
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 466
IP  - 7302
DP  - 2010 Jul 1
TI  - Genome-wide association study in alopecia areata implicates both innate and 
      adaptive immunity.
PG  - 113-7
LID - 10.1038/nature09114 [doi]
AB  - Alopecia areata (AA) is among the most highly prevalent human autoimmune 
      diseases, leading to disfiguring hair loss due to the collapse of immune 
      privilege of the hair follicle and subsequent autoimmune attack. The genetic 
      basis of AA is largely unknown. We undertook a genome-wide association study 
      (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single 
      nucleotide polymorphisms that are significantly associated with AA (P <or= 5 x 
      10(-7)). Here we show an association with genomic regions containing several 
      genes controlling the activation and proliferation of regulatory T cells (T(reg) 
      cells), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), interleukin 
      (IL)-2/IL-21, IL-2 receptor A (IL-2RA; CD25) and Eos (also known as Ikaros family 
      zinc finger 4; IKZF4), as well as the human leukocyte antigen (HLA) region. We 
      also find association evidence for regions containing genes expressed in the hair 
      follicle itself (PRDX5 and STX17). A region of strong association resides within 
      the ULBP (cytomegalovirus UL16-binding protein) gene cluster on chromosome 
      6q25.1, encoding activating ligands of the natural killer cell receptor NKG2D 
      that have not previously been implicated in an autoimmune disease. By probing the 
      role of ULBP3 in disease pathogenesis, we also show that its expression in 
      lesional scalp from patients with AA is markedly upregulated in the hair follicle 
      dermal sheath during active disease. This study provides evidence for the 
      involvement of both innate and acquired immunity in the pathogenesis of AA. We 
      have defined the genetic underpinnings of AA, placing it within the context of 
      shared pathways among autoimmune diseases, and implicating a novel disease 
      mechanism, the upregulation of ULBP ligands, in triggering autoimmunity.
FAU - Petukhova, Lynn
AU  - Petukhova L
AD  - Department of Dermatology, Columbia University, New York, New York 10032, USA.
FAU - Duvic, Madeleine
AU  - Duvic M
FAU - Hordinsky, Maria
AU  - Hordinsky M
FAU - Norris, David
AU  - Norris D
FAU - Price, Vera
AU  - Price V
FAU - Shimomura, Yutaka
AU  - Shimomura Y
FAU - Kim, Hyunmi
AU  - Kim H
FAU - Singh, Pallavi
AU  - Singh P
FAU - Lee, Annette
AU  - Lee A
FAU - Chen, Wei V
AU  - Chen WV
FAU - Meyer, Katja C
AU  - Meyer KC
FAU - Paus, Ralf
AU  - Paus R
FAU - Jahoda, Colin A B
AU  - Jahoda CA
FAU - Amos, Christopher I
AU  - Amos CI
FAU - Gregersen, Peter K
AU  - Gregersen PK
FAU - Christiano, Angela M
AU  - Christiano AM
LA  - eng
GR  - N01AR62279/HL/NHLBI NIH HHS/United States
GR  - R01 CA133996/CA/NCI NIH HHS/United States
GR  - R01 AR044422/AR/NIAMS NIH HHS/United States
GR  - R01AR56016/AR/NIAMS NIH HHS/United States
GR  - R01 AR056016-03/AR/NIAMS NIH HHS/United States
GR  - R01 AR056016/AR/NIAMS NIH HHS/United States
GR  - R01CA133996/CA/NCI NIH HHS/United States
GR  - R01 AR052579/AR/NIAMS NIH HHS/United States
GR  - P30CA016772/CA/NCI NIH HHS/United States
GR  - R01AR52579/AR/NIAMS NIH HHS/United States
GR  - R01AR44422/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, CD)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (IKZF4 protein, human)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (Qa-SNARE Proteins)
RN  - 0 (STX17 protein, human)
RN  - 0 (ULBP3 protein, human)
RN  - 148971-36-2 (Ikaros Transcription Factor)
RN  - EC 1.11.1.15 (PRDX5 protein, human)
RN  - EC 1.11.1.15 (Peroxiredoxins)
SB  - IM
MH  - Adaptive Immunity/*genetics/immunology
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Alopecia Areata/*genetics/immunology
MH  - Antigens, CD/genetics
MH  - Autoimmune Diseases/*genetics/immunology
MH  - CTLA-4 Antigen
MH  - Case-Control Studies
MH  - Female
MH  - GPI-Linked Proteins
MH  - *Genetic Predisposition to Disease
MH  - *Genome-Wide Association Study
MH  - Hair Follicle/cytology/immunology/metabolism
MH  - Humans
MH  - Ikaros Transcription Factor/genetics
MH  - Immunity, Innate/*genetics/immunology
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Interleukin-2 Receptor alpha Subunit/genetics
MH  - Male
MH  - Middle Aged
MH  - NK Cell Lectin-Like Receptor Subfamily K/immunology
MH  - Peroxiredoxins/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Qa-SNARE Proteins/genetics
MH  - T-Lymphocytes, Regulatory/cytology/immunology
PMC - PMC2921172
MID - NIHMS226472
EDAT- 2010/07/03 06:00
MHDA- 2010/08/07 06:00
PMCR- 2011/01/01
CRDT- 2010/07/03 06:00
PHST- 2010/01/26 00:00 [received]
PHST- 2010/04/22 00:00 [accepted]
PHST- 2010/07/03 06:00 [entrez]
PHST- 2010/07/03 06:00 [pubmed]
PHST- 2010/08/07 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - nature09114 [pii]
AID - 10.1038/nature09114 [doi]
PST - ppublish
SO  - Nature. 2010 Jul 1;466(7302):113-7. doi: 10.1038/nature09114.