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[Influence of CD14 gene polymorphism on the expression of high mobility group box-1 protein in patients with severe
Ning Dong1, Yong-ming Yao, Xian-jin Huang
1First Hospital Affiliated to the PLA General Hospital, Beijing 100048, China.
Objective:
To investigate the influence of the lipopolysaccharide receptor CD14-159C/T gene polymorphism on the synthesis and release of high mobility group box-1 protein (HMGB1), and its relation to sepsis in patients with severe burn.
Methods:
Venous blood from 35 patients with burn area equal to or larger than 30% TBSA was obtained on post burn day (PBD) 1, 3, 5, 7, 14, 21, and 28 respectively. Eleven volunteers were enrolled as healthy control group (HC).CD14-159C/T gene polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. Plasma level of HMGB1 was determined with ELISA. Leukocyte HMGB1 mRNA expression was determined with RT-PCR. Data were processed with chi(2) test, analysis of variance, and t test.
Results:
Among the C-159T genotype of CD14 gene in the 35 patients, the distribution frequency of the T and the C allele was respectively 57.2% and 42.8%. Seven cases (20.0%) were homozygous for the C allele (CC), 16 cases (45.7%) were heterozygous (TC), and 12 cases (34.3%) were homozygous for the T allele (TT). Allele and genotype frequencies in cases were testified as reaching the Hard-Weinberg equilibrium. The incidence of sepsis was markedly lower in CC homozygous patients than in TC heterozygous and TT homozygous patients. Only one of the 3 septic patients in CC homozygous type died; 4 of 9 septic cases in TC heterozygous type and 4 of 7 septic cases in TT homozygous type died. Plasma levels of HMGB1 of patients were significantly elevated early on PBD 1 as compared with HC group, and higher values were found in TC heterozygous and TT homozygous patients than that in CC homozygous patients on PBD 14, 21, 28 (with F value respectively 3.5671, 4.2035, 3.8529, P < 0.05 or P < 0.01). Higher HMGB1 mRNA expression was found in septic patients as compared with non-sepsis patients on PBD 14 (1.5 +/- 0.5 vs. 1.2 +/- 0.4, t = -2.205, P < 0.05). Plasma level of HMGB1 was also respectively higher in septic patients than in non-sepsis patients on PBD 7, 21 [(44 +/- 29) ng/mL vs. (26 +/- 12) ng/mL, t = -2.355, P < 0.05; (25 +/- 15) ng/mL vs. (10 +/- 6) ng/mL, t = -3.872, P < 0.01)].
Conclusions:
CD14C-159T gene polymorphism might markedly influence the synthesis and release of HMGB1, and it is associated with increase in susceptibility of sepsis in patients with severe burn.
