PMID- 19884265
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20161018
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 162
IP  - 2
DP  - 2010 Feb
TI  - Cytotoxic T lymphocyte antigen-4 Ala17 polymorphism is a genetic marker of 
      autoimmune adrenal insufficiency: Italian association study and meta-analysis of 
      European studies.
PG  - 361-9
LID - 10.1530/EJE-09-0618 [doi]
AB  - OBJECTIVE: Cytotoxic T lymphocyte antigen-4 (CTLA4) gene polymorphism has been 
      associated with human autoimmune diseases, but discordant data are available on 
      its association with autoimmune Addison's disease (AAD). We tested the human 
      leukocyte antigen (HLA)-independent association of CTLA4+49 (A/G) (Ala 17) and/or 
      CTLA4 CT60 (A/G) polymorphism with AAD. DESIGN: DNA samples from 180 AAD patients 
      and 394 healthy control subjects from continental Italy were analyzed, and 
      association statistical analyses and meta-analysis of published studies were 
      performed. Methods TaqMan minor groove binder chemistry assays and PCR fragment 
      length polymorphism assays were used. RESULTS: Frequency of allele G of CTLA4+49 
      was significantly increased among AAD patients (40% alleles) than among healthy 
      controls (27% alleles; P<0.0001). CTLA4 CT60 polymorphism was associated with AAD 
      only in the heterozygous A/G individuals. The frequency of +49 AG+GG genotypes 
      was significantly higher among AAD patients than among healthy control subjects, 
      in both a co-dominant (P<0.0001) and G dominant model (P<0.0001). CTLA4+49 allele 
      G was significantly associated with disease risk in both patients with isolated 
      AAD and in patients with autoimmune polyendocrine syndrome. Multivariate logistic 
      regression analysis showed that CTLA4+49 allele G was positively associated with 
      AAD (P<0.0001, odds ratio (OR)=2.43, 95% confidence interval=1.54-3.86) also 
      after correction for DRB1*03-DQA1*0501-DQB1*0201, DRB1*04-DQA1*0301-DQB1*0302, 
      and sex. Meta-analysis of five studies revealed a significant association of 
      CTLA4+49 allele G with AAD (P<0.0001) with an overall OR of 1.48 (1.28-1.71). 
      CONCLUSIONS: The CTLA4+49 polymorphism is strongly associated with genetic risk 
      for AAD, independently from the well-known association with HLA class II genes.
FAU - Brozzetti, Annalisa
AU  - Brozzetti A
AD  - Section of Internal Medicine and Endocrine and Metabolic Sciences, Department of 
      Internal Medicine, University of Perugia, Via Enrico Dal Pozzo, 06126 Perugia, 
      Italy.
FAU - Marzotti, Stefania
AU  - Marzotti S
FAU - Tortoioli, Cristina
AU  - Tortoioli C
FAU - Bini, Vittorio
AU  - Bini V
FAU - Giordano, Roberta
AU  - Giordano R
FAU - Dotta, Francesco
AU  - Dotta F
FAU - Betterle, Corrado
AU  - Betterle C
FAU - De Bellis, Annamaria
AU  - De Bellis A
FAU - Arnaldi, Giorgio
AU  - Arnaldi G
FAU - Toscano, Vincenzo
AU  - Toscano V
FAU - Arvat, Emanuela
AU  - Arvat E
FAU - Bellastella, Antonio
AU  - Bellastella A
FAU - Mantero, Franco
AU  - Mantero F
FAU - Falorni, Alberto
AU  - Falorni A
CN  - Italian Addison Network
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20091102
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Antigens, CD)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Genetic Markers)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Addison Disease/*epidemiology/*genetics/immunology
MH  - Alanine/genetics
MH  - Antigens, CD/*genetics/immunology
MH  - Autoimmune Diseases/*genetics/immunology
MH  - CTLA-4 Antigen
MH  - Genetic Markers
MH  - Humans
MH  - Italy/epidemiology
MH  - *Polymorphism, Genetic
MH  - Risk Factors
FIR - Ambrosi, B
IR  - Ambrosi B
FIR - Angeli, A
IR  - Angeli A
FIR - Baccarelli, A
IR  - Baccarelli A
FIR - Barbetta, L
IR  - Barbetta L
FIR - Basta, G
IR  - Basta G
FIR - Beck-Peccoz, P
IR  - Beck-Peccoz P
FIR - Bizzarro, A
IR  - Bizzarro A
FIR - Boscaro, M
IR  - Boscaro M
FIR - Calcinaro, F
IR  - Calcinaro F
FIR - Cavagnini, F
IR  - Cavagnini F
FIR - Celleno, R
IR  - Celleno R
FIR - Dal Pra, C
IR  - Dal Pra C
FIR - Ghigo, E
IR  - Ghigo E
FIR - Laureti, S
IR  - Laureti S
FIR - Libe, R
IR  - Libe R
FIR - Lore, F
IR  - Lore F
FIR - Mannelli, M
IR  - Mannelli M
FIR - Mantovani, G
IR  - Mantovani G
FIR - Paccotti, P
IR  - Paccotti P
FIR - Pecori Giraldi, F
IR  - Pecori Giraldi F
FIR - Perniola, R
IR  - Perniola R
FIR - Santeusanio, F
IR  - Santeusanio F
FIR - Terzolo, M
IR  - Terzolo M
FIR - Tiberti, C
IR  - Tiberti C
FIR - Toja, P
IR  - Toja P
FIR - Torlontano, M
IR  - Torlontano M
FIR - Trischitta, V
IR  - Trischitta V
FIR - Zanchetta, R
IR  - Zanchetta R
EDAT- 2009/11/04 06:00
MHDA- 2010/02/18 06:00
CRDT- 2009/11/04 06:00
PHST- 2009/11/04 06:00 [entrez]
PHST- 2009/11/04 06:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
AID - EJE-09-0618 [pii]
AID - 10.1530/EJE-09-0618 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2010 Feb;162(2):361-9. doi: 10.1530/EJE-09-0618. Epub 2009 Nov 
      2.