ECE2007 Oral Communications Thyroid clinical (7 abstracts)
CTLA- 4 gene polymorphisms and autoimmune thyroid diseases: meta-analyses of published and individual-level data
Fotini Kavvoura 1 , Takashi Akamizu 2 , Takuya Awata 3 , Yoshiyuki Ban 4 , Dimitry Chistiakov 5 , Irena Frydecka 6 , Abbas Ghaderi 7 , Stephen Gough 8 , Yuji Hiromatsu 9 , Rafal Ploski 10 , Pei-Wen Wang 11 , Yoshio Ban 4 , Tomasz Bednarczuk 12 , Emma Chistiakova 13 , Marcin Chojm 10 , Joanne Heward 8 , Hitomi Hiratani 2 , Suh-Hang Hank Juo 14 , Lidia Karabon 18 , Shigehiro Katayama 3 , Susumu Kurihara 3 , Rue-Tsuan Liu 11 , Ikuyo Miyake 9 , Gholam-Hossein Omrani 15 , Edyta Pawlak 18 , Matsuo Taniyama 16 , Teruaki Tozaki 17 & John PA Ioannidis 1
1Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; 2Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, Kyoto, Japan; 3Department of Medicine, Saitama Medical University, Saitama, Japan; 4Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; 5Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States; 6Department of Hematology, Medical Academy, Wroclaw, Poland; 7Shiraz Institute for Cancer Research, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; 8Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, United Kingdom; 9Kurume University School of Medicine, Kurume, Fukuoka, Japan; 10Human Molecular Genetics Laboratory of the Department of Forensic Medicine, Department of Medical Genetics, Medical University of War, Warsaw, Poland; 11Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 12Department of Endocrinology, Medical Research Center, Polish Academy of Science, Warsaw, Poland; 13Department of Molecular Diagnostics, National Research Center GosNIIgenetika, Moscow, Russia; 14Graduate Institute of Medical Genetics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 15Endocrine and Metabolism Research Center, Namazee Hospital, Shiraz, Iran; 16Division of Endocrinology and Metabolism, Showa University Fujigaoka Hospital, Yokohama, Kanagawa-ken, Japan; 17Department of Medical Information, Showa University School of Pharmaceutical Science, Showa, Japan; 18Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Background: 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.
Methodology/Principal findings: Meta-analyses of group-level data from 32 (n=11.019 subjects) and 12 (n=4.479) published and unpublished studies were performed for the association of the A49G polymorphism with GD and HT, respectively. Fifteen (n=7.246) and 6 (n=3.086) studies were available for the CT60 polymorphism, respectively. Meta-analyses of individual-level data from 10 (n=4.906 subjects) and 5 (n=2.386) collaborating teams for GD and HT, respectively, using haplotypes of both polymorphisms were also performed. Group-level data suggested significant associations with GD and HT for both A49G (odds ratio 1.49, P=6×10−14 and 1.29 [P=0.001] per G allele, respectively) and CT60 (OR 1.45, [P=2×10−9] 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% CI: 1.31–1.70) and 1.36 (95% CI: 1.16–1.59) for GD and HT, respectively. The AG haplotype also increased the risk of GD (1.35, 95% CI: 1.16–1.55) but not of HT (1.02, 95% CI: 0.71–1.47). The results for the GA haplotype were inconclusive. Data were consistent with a dose-response effect for the G-allele of CT60.
Conclusions/Interpretation: The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.
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Endocrine Abstracts
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