Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients

Ohmann, Erin; Brooks, Maria M.; Webber, Steven A.; Girnita, Diana M.; Ferrell, Robert E.; Burckart, Gilbert J.; Chinnock, Richard; Canter, Charles E.; Addonizio, Linda J.; Bernstein, Daniel; Kirklin, James K.; Naftel, David C.; Zeevi, Adriana

doi:10.1016/j.healun.2010.07.013

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…Several studies have examined the impact of differences in socioeconomic status (SES) and access to care by race as a means to explain these disparities and have concluded that these factors alone are not the sole cause . Genetic variation has been hypothesized to play a role in predisposition to certain posttransplant outcomes and drug‐related adverse effects . We have previously confirmed that the distributions of risk‐associated polymorphisms in several genes involved in immunogenicity and in drug disposition vary considerably by race/ethnicity .…”

Section: Introductionmentioning

confidence: 65%

“…In complex disorders, including therapeutic interventions such as transplantation, common genetic variations likely influence the occurrence, severity, and response to treatment of many clinical outcomes . We have previously investigated the influence of genetic polymorphisms on posttransplant outcomes within this SCCOR program using a candidate gene approach. Among a panel of 20 genes, we have studied over 30 genotypes.…”

Section: Discussionmentioning

confidence: 99%

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The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

Green

Brooks

Burckart

et al. 2017

American Journal of Transplantation

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Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

Green

Brooks

Burckart

et al. 2017

American Journal of Transplantation

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“…Data indicated that the +49A allele increases the risk of development of viral and parasitic diseases (e.g., dengue, Chagas disease and American cutaneous leishmaniasis) but confers resistance to autoimmune diseases (MG, PE) [22]. Ohmann et al [18] reported that SNP CTLA4 +49(rs231775) may be associated with late post-transplantation viral infection in pediatric heart recipients in the USA. For the SNP rs5742909 C/T, several studies have shown that the CC genotype is associated with viral disease and chronic HBV infection [23].…”

Section: Discussionmentioning

confidence: 99%

“…Ohmann et al [18] reported that SNP CTLA4 +49(rs231775) may be associated with late post-transplantation viral infection in pediatric heart transplant recipients in the USA.…”

Section: Introductionmentioning

confidence: 99%

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Guo

Wei

et al. 2013

PLoS ONE

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BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.

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“…These genetic variations have been shown to be associated with post-transplant infections [7,8], and might result in interindividual differences in response to immunotherapy targeting this molecule. These genetic variations have been shown to be associated with post-transplant infections [7,8], and might result in interindividual differences in response to immunotherapy targeting this molecule.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T-lymphocyte antigen 4 gene polymorphism influences the incidence of symptomatic human cytomegalovirus infection after renal transplantation

Misra

Pandey

Kapoor

et al. 2015

Pharmacogenetics and Genomics

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Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients

Cited by 10 publications

References 33 publications

The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Cytotoxic T-lymphocyte antigen 4 gene polymorphism influences the incidence of symptomatic human cytomegalovirus infection after renal transplantation

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