PMID- 27762046
OWN - NLM
STAT- MEDLINE
DCOM- 20171225
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 14
IP  - 12
DP  - 2016 Dec
TI  - Immunochip analysis identifies novel susceptibility loci in the human leukocyte 
      antigen region for acquired thrombotic thrombocytopenic purpura.
PG  - 2356-2367
LID - 10.1111/jth.13548 [doi]
AB  - Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura 
      (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by 
      Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant 
      rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and 
      HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to 
      hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura 
      SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, 
      life-threatening thrombotic microangiopathy associated with the development of 
      autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. 
      Similarly to what has been found for other autoimmune disorders, there is 
      evidence of a genetic contribution, including the association of the human 
      leukocyte antigen (HLA) class II complex with disease risk. Objective To identify 
      novel genetic risk factors in acquired TTP. Patients/Methods We undertook a 
      case-control genetic association study in 190 European-origin TTP patients and 
      1255 Italian healthy controls by using the Illumina Immunochip. Replication 
      analysis in 88 Italian cases and 456 controls was performed with 
      single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We 
      identified one common variant (rs6903608) located within the HLA class II locus 
      that was independently associated with acquired TTP at genome-wide significance 
      and conferred a 2.6-fold increased risk of developing a TTP episode (95% 
      confidence interval [CI] 2.02-3.27, P = 1.64 x 10(-14) ). We also found five 
      non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively 
      associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and 
      rs1334768 (nominal P-values ranging from 1.59 x 10(-5) to 7.60 x 10(-5) ). 
      Replication analysis confirmed the association of HLA variant rs6903608 with 
      acquired TTP (pooled P = 3.95 x 10(-19) ). Imputation of classic HLA genes 
      followed by stepwise conditional analysis revealed that the combination of 
      rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in 
      acquired TTP. Our results refined the association of the HLA class II locus with 
      acquired TTP, confirming its importance in the etiology of this autoimmune 
      disease.
CI  - (c) 2016 International Society on Thrombosis and Haemostasis.
FAU - Mancini, I
AU  - Mancini I
AUID- ORCID: 0000-0002-5059-5212
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, Milan, Italy.
FAU - Ricano-Ponce, I
AU  - Ricano-Ponce I
AD  - Genetics Department, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - Pappalardo, E
AU  - Pappalardo E
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, Milan, Italy.
FAU - Cairo, A
AU  - Cairo A
AD  - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' 
      Granda Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Gorski, M M
AU  - Gorski MM
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, Milan, Italy.
FAU - Casoli, G
AU  - Casoli G
AD  - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' 
      Granda Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Ferrari, B
AU  - Ferrari B
AD  - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' 
      Granda Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Alberti, M
AU  - Alberti M
AD  - IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Clinical Research 
      Center for Rare Diseases, Aldo e Cele Dacco, Bergamo, Italy.
FAU - Mikovic, D
AU  - Mikovic D
AD  - Hemostasis Department and Hemophilia Center, Blood Transfusion Institute of 
      Serbia, Belgrade, Serbia.
FAU - Noris, M
AU  - Noris M
AD  - IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Clinical Research 
      Center for Rare Diseases, Aldo e Cele Dacco, Bergamo, Italy.
FAU - Wijmenga, C
AU  - Wijmenga C
AD  - Genetics Department, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - Peyvandi, F
AU  - Peyvandi F
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, Milan, Italy.
AD  - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' 
      Granda Ospedale Maggiore Policlinico, Milan, Italy.
CN  - Italian Group of TTP Investigators
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161203
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - Thrombotic thrombocytopenic purpura, acquired
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Autoantibodies/immunology
MH  - Autoimmunity
MH  - Case-Control Studies
MH  - Chromosome Mapping
MH  - Europe
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DQ beta-Chains/*genetics
MH  - Humans
MH  - Italy
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Principal Component Analysis
MH  - Purpura, Thrombotic Thrombocytopenic/*genetics
MH  - Risk Factors
OTO - NOTNLM
OT  - SNPs
OT  - genetic association studies
OT  - genetic predisposition to disease
OT  - human leukocyte antigen
OT  - risk factors
OT  - thrombotic thrombocytopenic purpura
FIR - Rinaldi, E
IR  - Rinaldi E
FIR - Melpignano, A
IR  - Melpignano A
FIR - Campus, S
IR  - Campus S
FIR - Podda, R A
IR  - Podda RA
FIR - Caria, C
IR  - Caria C
FIR - Caddori, A
IR  - Caddori A
FIR - Di Francesco, E
IR  - Di Francesco E
FIR - Giuffrida, G
IR  - Giuffrida G
FIR - Agostini, V
IR  - Agostini V
FIR - Roncarati, U
IR  - Roncarati U
FIR - Mannarella, C
IR  - Mannarella C
FIR - Fragasso, A
IR  - Fragasso A
FIR - Podda, G M
IR  - Podda GM
FIR - Bertinato, E
IR  - Bertinato E
FIR - Cerbone, A M
IR  - Cerbone AM
FIR - Tufano, A
IR  - Tufano A
FIR - Loffredo, G
IR  - Loffredo G
FIR - Poggi, V
IR  - Poggi V
FIR - Pizzuti, M
IR  - Pizzuti M
FIR - Re, G
IR  - Re G
FIR - Ronchi, M
IR  - Ronchi M
FIR - Codeluppi, K
IR  - Codeluppi K
FIR - Facchini, L
IR  - Facchini L
FIR - De Fanti, A
IR  - De Fanti A
FIR - Amarri, S
IR  - Amarri S
FIR - Trisolini, S M
IR  - Trisolini SM
FIR - Capria, S
IR  - Capria S
FIR - Aprile, L
IR  - Aprile L
FIR - Defina, M
IR  - Defina M
FIR - Ceru, S
IR  - Ceru S
EDAT- 2016/10/21 06:00
MHDA- 2017/12/26 06:00
CRDT- 2016/10/21 06:00
PHST- 2016/03/01 00:00 [received]
PHST- 2016/07/28 00:00 [accepted]
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2017/12/26 06:00 [medline]
PHST- 2016/10/21 06:00 [entrez]
AID - S1538-7836(22)02547-8 [pii]
AID - 10.1111/jth.13548 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2016 Dec;14(12):2356-2367. doi: 10.1111/jth.13548. Epub 2016 
      Dec 3.