Association of Genetic Variation in Inducible Costimulator Gene With Outcome of Kidney Transplantation

Haimila, Katri; Turpeinen, Hannu; Alakulppi, Noora; Kyllönen, L.; Salmela, K.; Partanen, Jukka

doi:10.1097/tp.0b013e318192897a

Cited by 40 publications

(52 citation statements)

References 17 publications

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“…In the present study, we extended our investigation to subsequent ICOS gene polymorphisms which were recently described as functional ones [17,19] and were shown to be associated with susceptibility to multiple sclerosis [19] and outcome after renal [18] or hematopoietic stem cell transplantation [29], but not to melanoma [30]. [19], the frequency of the AA genotype was significantly lower in MS patients with relapsing-remitting disease than in controls, and those patients had a lower relapse rate and MS severity score.…”

Section: Discussionmentioning

confidence: 89%

“…The ICOSc.602A>C and ICOSc.1624C>T polymorphisms have been described as susceptibility markers of outcome after renal transplantation [18] and hematopoietic stem cell transplantation [29] Additionally, we included the ICOS ISV1+173T>C polymorphism in our study, which does not influence ICOS mRNA level in CD4 + cells but, since this polymorphism is located near the CTLA-4 gene, variations at that position influence CTLA-4 mRNA expression for both CTLA-4 isoforms, the soluble and full length (membrane) [17].…”

Section: Discussionmentioning

confidence: 99%

“…Several polymorphisms have been found in the ICOS gene: two microsatellite in the fourth intron and 31 single-nucleotide polymorphisms (SNPs) (http:// //www.hapmap.org). None of the described ICOS SNPs leads to changes in amino acid, while a few have been demonstrated to be functional variants [17][18][19][20]. The chromosomal region of 2q33 harboring the CD28, CTLA-4, and ICOS gene family has been described as carrying predisposing genes for several autoimmune diseases [19,[21][22][23] and, recently, for cancer [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Karabon¹,

Jedynak²,

Tomkiewicz³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan ® SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Karabon¹,

Jedynak²,

Tomkiewicz³

et al. 2011

Folia Histochem Cytobiol.

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“…An association with outcome of kidney transplantation was reported in seven genetic studies (Slavcheva et al, 2001;Gendzekhadze et al, 2006;Wisniewski et al, 2006;Gorgi et al, 2006;Kusztal et al, 2007Kusztal et al, , 2010Kim et al, 2010). On the other hand, four studies did not succeed in replicating the association with CTLA4 (Dmitrienko et al, 2005;Haimila et al, 2009b;Krichen et al, 2009Krichen et al, , 2010. The SNP CTLA4+49 A/G (rs231775) is the most frequently studied variant and most often found to be associated.…”

Section: Co-stimulator Receptor Genes May Predispose To the Poor Outcmentioning

confidence: 99%

“…Two of the genetic variants of CD28 were included in three different association studies but no association was found (Haimila et al, 2009b;Krichen et al, 2009;Kusztal et al, 2010). CTLA4 gene polymorphisms have been examined in relation to kidney transplantation in a few studies (Table2).…”

Section: Co-stimulator Receptor Genes May Predispose To the Poor Outcmentioning

confidence: 99%

Immune Gene Polymorphisms Associate with Outcome in Kidney Transplantation

Haimila¹,

Alakulppi²,

Partanen³

2011

Kidney Transplantation - New Perspectives

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Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

et al. 2012

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Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene polymorphisms have been reported to influence the risk for acute rejection (AR) in transplant recipients. However, the results still remain controversial and ambiguous. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of AR in transplant recipients. Electronic searches for all publications were conducted on associations between this variant and acute rejection in Medline and Embase databases through November 2011. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 18 case-control studies from ten articles were analyzed. This meta-analysis included 2,081 cases of transplant recipients in which 813 cases developed AR and 1,268 cases did not develop AR. The results indicated that there was no statistically significant association between the risk of AR and the +49A/G polymorphism or the -318C/T polymorphism (+49A/G: OR = 0.876, 95 % CI = 0.650-1.180 for GG vs. AA; OR = 1.121, 95 % CI = 0.911-1.379 for AG + GG vs. AA; -318C/T: OR = 0.397, 95 % CI = 0.138-1.143 for TT vs. CC; OR = 0.987, 95 %CI = 0.553-1.760 for CT + TT vs. CC). However, individuals who carried CT60 A allele might have a decreased risk of AR (AA vs. GG OR = 0.535, 95 % CI = 0.340-0.841, A vs. G OR = 0.759, 95 % CI = 0.612-0.914) in liver transplant recipients among Europeans, but because only two studies were included, so the result should be caution. In further stratified analyses for the +49A/G and the -318C/T polymorphisms, no obvious significant associations were found in subgroups of renal transplant recipients and Europeans, a reduced incidence of acute rejection was observed in liver transplant recipients that are homogenous for +49G (OR = 0.638, 95 % CI = 0.427-0.954 for GG vs. AA/AG), while this has not been observed in renal transplant recipients. Overall this meta-analysis suggests that +49A/G and the -318C/T polymorphisms in CTLA-4 may be not associated with the risk of rejection after organ transplantation, but CTLA +49A/G and +6230G/A polymorphisms may be associated with acute rejection after liver transplantation, not after renal transplantation. In future, more studies should be included to evaluate the association between +6230G/A polymorphism and AR risk.

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Association of Genetic Variation in Inducible Costimulator Gene With Outcome of Kidney Transplantation

Abstract: The present results indicate that potentially functional genetic variation in T-cell costimulatory molecule ICOS has an effect on the outcome of kidney transplantation.

Cited by 40 publications

References 17 publications

<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Immune Gene Polymorphisms Associate with Outcome in Kidney Transplantation

Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

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