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

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Abstract

Background

The role of CTLA4 gene polymorphisms in T-cell-mediated immunity in association with human cytomegalovirus (HCMV) infection after transplantation is poorly understood. In the present study, we have made an attempt to investigate the impact of CTLA4 single nucleotide polymorphisms (SNPs) (rs231775, rs5742909, rs11571317, rs16840252, rs4553808, rs3087243) and dinucleotide (AT)n repeat polymorphism on the incidence of symptomatic HCMV infection (disease) among 270 renal allograft recipients.

Materials and methods

Genotyping of CTLA4 SNPs was performed by a PCR, followed by a restriction fragment length polymorphism assay. The detection of the dinucleotide (AT)n repeat polymorphism was carried out by PCR-polyacrylamide gel electrophoresis.

Results

An almost three-fold increased risk was observed for the incidence of symptomatic HCMV infection in mutant genotype carriers of rs231775 and rs3087243 SNPs under additive and recessive models, respectively. The mutant haplotype carriers of six studied SNPs (rs231775, rs5742909, rs11571317, rs16840252, rs4553808 and rs3087243) showed an almost two-fold higher risk for symptomatic HCMV cases, whereas wild-type haplotype combinations of these six SNPs showed a protective effect. Subsequently, no correlation was observed in the promoter region SNPs of CTLA4, namely, rs5742909, rs11571317, rs16840252 and rs4553808 in symptomatic HCMV cases at the genotypic/allelic level. Survival analysis showed that the mutant genotypes of rs231775 and rs3087243 SNPs were associated with the lowest HCMV disease-free survival compared with heterozygous and wild genotypes. The crude and adjusted hazard ratios showed an almost three-fold and 2.5-fold increased risk in univariate and multivariate Cox regression models, respectively, for HCMV disease-free survival against mutant genotypes of rs231775 and rs3087243 SNPs. CTLA4 dinucleotide (AT)n repeat analysis showed that the smaller allele (102 bp) was associated with a protective effect, whereas the longer (110 and 116 bp) alleles showed a susceptible effect for symptomatic HCMV cases.

Conclusion

These results suggested that CTLA4 variants might be involved in the clinical manifestation of HCMV diseases.

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