Open AccessTHE RISK OF EARLY LIVER ALLOGRAFT DYSFUNCTION IS ASSOCIATED WITH THE TLR-4 GENE GENOTYPE IN THE RS913930 SEQUENCE AND IS IMPLEMENTED VIA HMGB1 NUCLEAR PROTEIN, KUPFFER CELLS AND IL-23 ACTIVATION
Author(s) -
А. Е. Щерба,
Anatoly Kustanovich,
A. I. Kireyeva,
D. Yu. Efimov,
С. В. Коротков,
А. Ф. Минов,
O. A. Lebedz,
Alla Koritko,
Dzmitry Fedoruk,
Eugeny Santotsky,
A. M. Dzyadzko,
О. О. Руммо
Publication year - 2016
Publication title -
vestnik transplantologii i iskusstvennyh organov
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.137
H-Index - 5
eISSN - 2412-6160
pISSN - 1995-1191
DOI - 10.15825/1995-1191-2016-3-22-30
Subject(s) - genotype , liver transplantation , transplantation , allele , single nucleotide polymorphism , minor allele frequency , snp , gastroenterology , medicine , biology , immunology , gene , genetics
Aim. To evaluate the associations of genotypes of clinically relevant nucleotides rs11536865, rs913930 and rs5030717 of the TLR-4 gene with the risk of development and severity of early allograft dysfunction after liver transplantation. Materials and methods. A case-control study enrolling 71 patients was organized. Inclusion criteria: DBD liver transplantation. Exclusion criteria: living related liver transplantation, reduced graft transplantation, recipient’s age fewer than 18. Results. Within rs5030717 there were identifi ed three genotypes: AA (81.6%) and two genotypes with the minor G-allele: AG (12.6%) and GG (5.6%). Within rs913930 there identi- fi ed three genotypes: TT (59.1%) and two genotypes with the minor C-allele: C/T (29.5%) and CC (11.2%). The rs11536865 studying revealed no polymorphism (GG genotype). The early allograft liver dysfunction (EAD) developed in 19.7% of patients, the severe EAD in 11.2% of patients, septic complications in 14%, acute cellular rejection in 23.9% of cases. The C/T genotype of the TLR-4 gene in the SNP rs913930 sequence was closely associated with the EAD development (OR 4.8 to 1; p = 0.047; 95% CI 1–23.4). Рatients with the donor’s liver C/T genotype had a reliably higher proportion (%) of the HMGB1 positive hepatocytes in the donor’s bioptate, 21 (17–29%) vs the СС+TT genotypes, 16 (10–19%) (Mann–Whitney test, p = 0.01). The CD68 expression in the liver bioptate at the donor’s stage was reliably higher in the carriers of heterozygotes in the SNP rs913930 (C/T genotype) and in the SNP rs5030717 (AG genotype), (Mann–Whitney test, p = 0.03). Signifi cant positive correlation between the CD68 expression in the donor’s liver bioptates and the IL-23 level in the hepatic vein has been determined in an hour after the portal reperfusion (ρ = 0.62; p = 0.04) as well as between the HMGB1 expression in the donor’s liver bioptates and the АSТ level in 24 hours after the reperfusion (r = 0.4; p = 0.02). The HMGB1 staining in the donor’s liver bioptates was higher in the EAD patients, 21 (20; 29) cells/mm2 in comparison with the patients without EAD, 16 (12; 18) (Mann–Whitney test, p = 0.0036). Conclusion. The early allograft liver dysfunction is associated with the genetic predisposition caused by the TLR-4 gene polymorphism and is implemented via the HMGB1, Kupffer cells and IL-23 activation.