The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes

Abstract

Background: The surveillance of kidney transplant patients depends on function of different immunologic markers like co-stimulatory molecules. These molecules may also be associated with post kidney transplant viral related outcomes.

Objectives: The aim of this study was to investigate the possible associations between co-stimulatory molecule gene polymorphisms and viral infections in kidney transplant patients.

Patients and methods: In total, 172 kidney transplant patients were included in this study. Single nucleotide polymorphisms in loci of co-stimulatory molecules including: PDCD.1, CD28, CTLA4 and ICOS, were analyzed in the studied patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Active Cytomegalovirus (CMV) infection and history of hepatitis C virus (HCV) infection were analyzed in each kidney transplant patient using the CMV antigenemia kit and HCV antibody assay, according to the manufacturer's instructions.

Results: CMV active infection was found in 31 of 172 (18.02%) kidney transplant patients. HCV infection was only found in two of the 172 (1.16%) studied patients. Significant associations were found between TT and TC genotypes of CTLA4 -1722T/C and T allele with acute rejection in CMV infected kidney transplant patients. A significant association was also found between the T allele of CD28 + 17 C/T genetic polymorphism and acute rejection in CMV infected kidney transplant patients. Significantly higher frequency of AA genotype and A allele of CTLA4 + 49AG polymorphism were found in CMV infected female patients. Also a significantly higher frequency of GG genotype and G allele of PDCD-1.3A/G polymorphisms were found in CMV infected female patients.

Conclusions: Based on these results, CTLA4 and CD28 genetic polymorphisms, which regulate T-cell activation, can influence active CMV infection in kidney transplant patients. These results should be confirmed by further investigations.

Keywords: Costimulatory Molecules; Cytomegalovirus; Hepatitis C Virus; Kidney Transplantation.

Figure 1.. Linkage Disequilibrium (LD) Plot of Co-stimulatory Molecule Polymorphisms in D’ Value in CMV Infected and Non-Infected Kidney Transplant Patients

D’ values are multiplied by 100, for example; 100 in some boxes means a D’ of 1. Dark color boxes are representative of high LD and light color boxes indicate low LD. The left upper boxes indicate P values of less than 0.05.