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Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

ABSTRACT: Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFN?4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFN?4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-?G/?G), 35% (CC-TT/TT) and 29.2% (CT-TT/?G) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFN?4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-?G/?G (83%) population with respect to CC-TT/TT (21%) and CT-TT/?G (40%) patients. Our data suggest a negative role of TT-?G/?G genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.

SUBMITTER: Annibali O

PROVIDER: S-EPMC6056038 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

Annibali Ombretta O Piccioni Livia L Tomarchio Valeria V Circhetta Erika E Sarlo Chiara C Franceschini Luca L Cantonetti Maria M Rizzo Emanuela E Angeletti Silvia S Tirindelli Maria Cristina MC Scagnolari Carolina C Statzu Maura M Avvisati Giuseppe G Riva Elisabetta E

PloS one 20180723 7

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The ...[more]

PMID: 30036376

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Project description:BACKGROUND:Tacrolimus is the first-line immunosuppressant after organ transplantation. It is mainly metabolized by cytochrome P450, family 3, subfamily A (CYP3A) enzymes, but there are large individual differences in metabolism. Interleukin 6 (IL6) has been shown to cause a pan-suppression of mRNA levels of ten major CYP enzymes in human hepatocyte cultures. IL6 has been shown to provide hepatoprotection in various models of liver injury. Rs1800796 is a locus in the IL6 gene promoter region which regulates cytokine production. We speculated that IL6 rs1800796 polymorphisms may lead to individual differences in tacrolimus metabolism by affecting CYP3A enzymes levels and liver function after liver transplantation. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-six liver transplant patients receiving tacrolimus were enrolled in the study. Two single nucleotide polymorphisms (SNP), CYP3A5 rs776746 and IL6 rs1800796, were genotyped in both donors and recipients. The effects of SNPs on tacrolimus concentration/dose (C/D ratio) at four weeks after transplantation were studied, as well as the effects of donor IL6 rs1800796 polymorphisms on liver function. Both donor and recipient CYP3A5 rs776746 allele A showed association with lower C/D ratios, while donor IL6 rs1800796 allele G showed an association with higher C/D ratios. Donor CYP3A5 rs776746 allele A, IL6 rs1800796 allele C, and recipient CYP3A5 rs776746 allele A were associated with fast tacrolimus metabolism. With increasing numbers of these alleles, patients were found to have increasingly lower tacrolimus C/D ratios at time points after transplantation. Donor IL6 rs1800796 allele G carriers showed an association with higher glutamic-pyruvic transaminase (GPT) levels. CONCLUSIONS:Combined analysis of donor CYP3A5 rs776746, IL6 rs1800796, and recipient CYP3A5 rs776746 polymorphisms may distinguish tacrolimus metabolism better than CYP3A5 rs776746 alone. IL6 may lead to individual differences in tacrolimus metabolism mainly by affecting liver function.

Project description:Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the >76 kbp, mean nucleotide diversity expressed as Watterson's theta was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r(2)) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency >0.10) SNPs, were identified.

Dataset Information

Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

Publications

Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

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