Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to chronic hepatitis B

Alizadeh, Amir Houshang Mohammad; Hajilooi, Mehrdad; Ranjbar, Mahdy; Fallahian, Farahnaz; Mousavi, Seyed Mohsen

doi:10.3748/wjg.v12.i4.630

Cited by 30 publications

(27 citation statements)

References 19 publications

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“…41 The diversity in a HBV clinical course was largely related to the host immunologic genetic variety especially costimulatory molecules which have roles in immune responses. 10,11,9,42 Therefore according to, the importance of costimulatory molecules, in this study their genetic variations was evaluated in allogeneic and autologous HSCT patients with and without HBV. The CTLA-4 preserves T-cell homeostasis and induces Fas-independent apoptosis of activated T cells elicited.…”

Section: Discussionmentioning

confidence: 99%

“…12 Several reports have shown that CTLA-4 gene polymorphisms may be associated with the susceptibility and chronicity of the disease in HBV-infected patients; however, the results are controversial. [9][10][11][12] Gu and associates reported that the A allele instead of CTLA4 49A/G (rs231775) polymorphisms enhances the inhibitory effect on T-cell activation, and the A/G variant may decrease the HBV clearance capability of T cells; thus, increasing HBV-related HCC susceptibility. 12 Duan and associates evaluated the CTLA-4 49A/G and 318 T/C polymorphisms in 172 chronic HBV-infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…9 Alizadeh et al and Schott et al have shown a significant association between CTLA-4 -318 C/T with a susceptibility to chronic HBV infection. 10,11 Jiang and associates showed that the GG genotype of the CTLA-4 49A/G in Chinese liver transplant patients is related to a reduced risk of the HBV recurrence. 43 Han and associates have shown a relation between the GG genotype of the CTLA-4 49A/G, with the lower TNF-α and IFN-γ levels in patients with chronic HBV infection.…”

Section: Ramin Yaghobi Et Al/experimental and Clinical Transplantatiomentioning

confidence: 99%

“…8 Cytotoxic T-lymphocyte antigen-4 gene polymorphisms, which may affect the function of CTLA4 in regulating the immune response, has been proposed to affect the susceptibility and chronicity of the disease in patients with HBV infection; however, the results are still controversial. [9][10][11][12]2 Similar to CTLA4, CD28 also binds to B7 family of receptors (CD80 and CD86), but it provides a positive costimulatory signal for T-cell proliferative response after being expressed on T cells. 13,14 Several polymorphisms in the CD28 gene may affect the intensity of T-cell-mediated immunity, resulting in various autoimmune diseases, and the occurrence of post transplant allograft rejection.…”

Section: Introductionmentioning

confidence: 99%

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Yaghobi

Saadi²,

Karimi³

et al. 2014

Exp Clin Transplant

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ramin Yaghobi Et Al/experimental and Clinical Transplantatiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Yaghobi

Saadi²,

Karimi³

et al. 2014

Exp Clin Transplant

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“…5 CTLA-4 Ϫ318 is also possibly associated with susceptibility to chronic hepatitis B. 6 This SNP has not been found to be associated with liver rejection following transplantation. 7,8 In this present work, Tapirdamaz et al updated their previous single-center study 7 with a retrospective multicenter study to determine the influence of the SNPs CTLA-4 ϩ49A/G and CTLA-4 ϩ6230G/A on the probability of rejection after liver transplantation.…”

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confidence: 99%

The influence of CTLA-4 gene polymorphisms on liver transplant outcomes

Perkins

2006

Liver Transpl

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;55:863-868. Abstract Background: The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene encodes for a membrane bound (mCTLA-4) and a soluble sCTLA-4 isoform, which are both involved in regulation of T cell function. The CTLA-4 ϩ49A/G single nucleotide polymorphism (SNP) influences expression of mCTLA-4; ϩ6230G/A SNP affects the production of soluble sCTLA-4. Aim: To examine whether these functional SNPs influence the rate of rejection after liver transplantation. Patients and methods: Liver graft recipients (n ϭ 483) were genotyped for both SNPs, and haplotypes were reconstructed. Association with rejection was tested by the log rank test using the Kaplan-Meier method with time to the first acute rejection episode as outcome. Multiple analysis of SNPs together with demographic factors was performed by Cox regression. Results: Three haplotypes were observed in the cohort: ϩ49A/ϩ6230A, ϩ49A/ϩ6230G, and ϩ49G/ϩ6230G. The ϩ49A/ϩ6230G haplotype was significantly and dose dependently associated with acute rejection (p ϭ 0.01). Of the demographic factors tested, only underlying liver disease was significantly associated with rejection. Adjusted for underlying liver disease, each additional ϩ49A/ϩ6230G haplotype allele resulted in a significantly higher risk of acute rejection (risk ratio 1.34 (95% confidence interval 1.04-1.72); p ϭ 0.02). Patients who lacked this haplotype had the lowest, carriers an intermediate, and homozygotes the highest risk of acute rejection. Conclusion: The CTLA-4 ϩ49A/ϩ6230G haplotype, which encodes for normal mCTLA-4 expression but reduced sCTLA-4 production, is a co-dominant risk allele for acute rejection after clinical liver transplantation. This implies that even under immunosuppression, CTLA-4 is critically involved in the regulation of the human immune response to allogeneic grafts. COMMENTSResearch on the influence of gene polymorphisms in the development of various disease states has flourished in

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CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with −318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients

et al. 2010

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Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) plays a pivotal role in regulating T cell activation, which is believably critical for the outcome of hepatitis B virus (HBV) infection. The expression and function of CTLA-4 may be affected by gene polymorphisms. This study investigated the influence of CTLA-4 polymorphisms on disease susceptibility in Chinese Han patients with chronic HBV infection. CTLA-4 +49A/G and -318C/T polymorphisms were evaluated by DNA amplification with polymerase chain reaction followed by the restriction fragment length polymorphism analysis. The patients with chronic HBV infection had higher frequencies of genotype AA and allele A of CTLA-4 +49A/G polymorphism. The haplotype +49A-318C was significantly over-represented (P < 0.001) and haplotype +49G-318C under-represented (P = 0.006) in the patients. The +49GG genotype was more frequent (P = 0.009) and +49A allele was less frequent in patients with lower ALT levels (P = 0.012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients.

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Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to chronic hepatitis B

Cited by 30 publications

References 19 publications

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The influence of CTLA-4 gene polymorphisms on liver transplant outcomes

CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with −318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients

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