Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: a meta-analysis.
BACKGROUND
Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) polymorphisms have been widely examined for their associations with autoimmune thyroid diseases [Graves' disease (GD) and Hashimoto thyroiditis (HT)], but their relative population effect remains unclear.


OBJECTIVE
The aim was to generate large-scale evidence on whether the CTLA-4 polymorphisms (A49G and CT60) and haplotypes thereof increase the susceptibility to GD and/or HT.


METHODS
Meta-analyses of group-level data were reviewed from 32 (11,019 subjects) and 12 (4,479) published and unpublished studies for the association of the A49G polymorphism with GD and HT, respectively (PubMed and HuGeNet search until July 2006). There were 15 (n = 7246) and six (n = 3086) studies available for the CT60 polymorphism, respectively. Meta-analyses of individual-level data from 10 (4906 subjects) and five (2386) collaborating teams for GD and HT, respectively, were also reviewed.


METHODS
Association of gene variants and haplotypes with GD and HT was measured.


RESULTS
Group-level data suggested significant associations with GD and HT for both A49G [odds ratios 1.49 (P = 6 x 10(-14)) and 1.29 (P = 0.001) per G allele, respectively] and CT60 [1.45 (P = 2 x 10(-9)) and 1.64 (P = 0.003) per G allele, respectively]. Results were consistent between Asian and Caucasian descent subjects. Individual-level data showed that compared with the AA haplotype, the risk conferred by the GG haplotype was 1.49 (95% confidence interval 1.31,1.70) and 1.36 (95% confidence interval 1.16,1.59) for GD and HT, respectively. Data were consistent with a dose-response effect for the G allele of CT60.


CONCLUSIONS
The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.
Kavvoura
Fotini K
FK
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.
Akamizu
Takashi
T
Awata
Takuya
T
Ban
Yoshiyuki
Y
Chistiakov
Dimitry A
DA
Frydecka
Irena
I
Ghaderi
Abbas
A
Gough
Stephen C
SC
Hiromatsu
Yuji
Y
Ploski
Rafal
R
Wang
Pei-Wen
PW
Ban
Yoshio
Y
Bednarczuk
Tomasz
T
Chistiakova
Emma I
EI
Chojm
Marcin
M
Heward
Joanne M
JM
Hiratani
Hitomi
H
Juo
Suh-Hang Hank
SH
Karabon
Lidia
L
Katayama
Shigehiro
S
Kurihara
Susumu
S
Liu
Rue-Tsuan
RT
Miyake
Ikuyo
I
Omrani
Gholam-Hossein R
GH
Pawlak
Edyta
E
Taniyama
Matsuo
M
Tozaki
Teruaki
T
Ioannidis
John P A
JP
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People; D060908:CTLA-4 Antigen; D002874:Chromosome Mapping; D030541:Databases, Genetic; D004305:Dose-Response Relationship, Drug; D018628:Gene Dosage; D006111:Graves Disease / Q000235:genetics; D006239:Haplotypes; D050031:Hashimoto Disease / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D044465:White People
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human