Article

The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves’ disease in the Chinese population

BMC Medical Genetics (Impact Factor: 2.08). 04/2013; 14(1):46. DOI: 10.1186/1471-2350-14-46
Source: PubMed

ABSTRACT

Background
The associations between the polymorphisms in Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) gene and Graves’ disease (GD) have been extensively investigated in Chinese population. However, the results were inconsistent. The objective of this study is to investigate the associations between the polymorphisms in CTLA-4 gene and the risk of GD by meta-analysis.

Methods
We searched Pubmed database, Medline (Ovid) database, CNKI database and Wanfang database, covering all studies until August 11, 2012. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software.

Results
A total of 28 case–control studies concerning the most widely studied three polymorphisms [+49A/G(rs231775), -318C/T(rs5742909) and CT60(rs3087243)] for Chinese population in 21 publications were included. The results suggested that the G allele carriers (GG+GA) might have an increased risk of GD when compared with the AA homozygote carriers for the +49A/G polymorphism (GG+GA vs. AA: OR = 2.57, 95%CI = 1.87-3.52). However, as to the -318C/T polymorphism and CT60 polymorphism, the results indicated that the variant allele carriers might have decreased risks of GD when compared with the homozygote carriers (−318C/T: TT+TC vs. CC: OR = 0.78, 95%CI = 0.62-0.97; CT60: AA+AG vs. GG: OR = 0.64, 95%CI = 0.52-0.78).

Conclusions
The current meta-analysis indicated that the polymorphisms in the CLTA-4 gene might be risk factors for GD in the Chinese population. In future, more large-scale case–control studies are needed to validate these results.

Download full-text

Full-text

Available from: Jiqiao Yang, Jul 18, 2014
  • Source
    • " auto - immune disease . Polymorphisms in cytotoxic T - lymphocyte anti - gen - 4 ( CTLA - 4 ) , acid phosphatase locus 1 ( ACP1 ) , Discs large homolog 5 ( DLG5 ) , interleukin - 10 ( IL - 10 ) , and apolipoprotein E ( APOE ) are commonly observed . Genetic A / G polymorphisms in CTLA - 4 have been identified in AS ( Huang et al . , 2014 ) , GD ( Du et al . , 2013 ) , and T / C polymorphisms may be associated with SLE risk ( Zhu et al . , 2013 ) . By contrast , there is no evidence to suggest that CTLA - 4 polymorphisms confer susceptibility to MS ( Gyu Song and Ho Lee , 2013 ) . While the majority of studies that investigate CTLA - 4 polymorphisms in autoimmune disease do not necessarily conside"
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.
    Full-text · Article · Apr 2014 · Frontiers in Neuroendocrinology
  • Source
    • " auto - immune disease . Polymorphisms in cytotoxic T - lymphocyte anti - gen - 4 ( CTLA - 4 ) , acid phosphatase locus 1 ( ACP1 ) , Discs large homolog 5 ( DLG5 ) , interleukin - 10 ( IL - 10 ) , and apolipoprotein E ( APOE ) are commonly observed . Genetic A / G polymorphisms in CTLA - 4 have been identified in AS ( Huang et al . , 2014 ) , GD ( Du et al . , 2013 ) , and T / C polymorphisms may be associated with SLE risk ( Zhu et al . , 2013 ) . By contrast , there is no evidence to suggest that CTLA - 4 polymorphisms confer susceptibility to MS ( Gyu Song and Ho Lee , 2013 ) . While the majority of studies that investigate CTLA - 4 polymorphisms in autoimmune disease do not necessarily conside"
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.
    Full-text · Article · Jan 2014 · Frontiers in Neuroendocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytotoxic T-Lymphocye Antigen 4 (CTLA-4) or CD152 is an inhibitory molecule that plays a critical role in maintenance of tolerance to self-antigens. CTLA-4 is structurally as well as functionally related to CD28, since it shares 31% of homology and binds the B7 family molecules CD80 and CD86 with higher affinity. Nevertheless, CTLA-4 have opposing effects on T cell activation and current evidence shows that its inhibitory role goes beyond the ligand-binding interaction. CTLA-4 competes with CD28 in binding to B7, interacts within the immunological synapsis elements and with clathrin adaptor proteins and tyrosine phosphatases through its cytoplasmic domain to regulate cell trafficking and to set the activation threshold within T cells. Moreover, we have learned from the knock out model that CTLA-4 plays a key role in regulatory T cells and in central tolerance. Because of its importance in maintenance of peripheral tolerance, CTLA-4 has been implicated in several autoimmune diseases, as systemic lupus erythematosus. Multiple single-nucleotide polymorphisms have been located to human Ctla-4 gene, and their association with autoimmune disease is still a matter of controversy. Despite the promising results of abatacept or CTLA-4-Ig in rheumatoid arthritis and murine lupus nephritis, more clinical randomized trials and standardization of outcomes are needed to prove its efficacy and safety in human lupus nephritis.
    No preview · Article · Jul 2013 · Autoimmunity reviews
Show more