polymorphic variants in exon 8 at the 3 utr of the hla-g gene are associated with septic shock in critically ill patients多态变异在3外显子8 utr hla-g基因与脓毒性休克相关联的危重病人.pdf

Graebin et al. Critical Care 2012, 16:R211 /content/16/5/R211 RESEARCH Open Access Polymorphic variants in exon 8 at the 3’ UTR of the HLA-G gene are associated with septic shock in critically ill patients 1,2 1 2 3 1* Pietra Graebin , Tiago D Veit , Clarice S Alho , Fernando S Dias and José AB Chies Abstract Introduction: Critically ill patients are characterized as individuals hospitalized in the Intensive Care Unit (ICU) and can evolve to sepsis, septic shock or even death. Among others, genetic factors can influence the outcome of critically ill patients. HLA-G is a non-classical class Ib molecule that has limited protein variability, presenting seven isoforms generated by alternative splicing, and presents immunomodulatory properties. Polymorphisms at the 3’UTR are thought to influence HLA-G gene expression. It was previously observed that increased sHLA-G5 levels were predictive of survival among septic shock patients. We assessed the frequencies of 7 polymorphisms in exon 8 at the 3’ UTR of HLA-G and associated these variants with different clinical outcomes in critically ill patients. Methods: Exon 8 at the 3’ UTR of the HLA-G gene from 638 critically ill subjects was amplified by PCR and sequenced. Genotypes were identified using FinchTV software v.1.4.0 and the most probable haplotype constitution of each sample was determined by PHASE software v.2.1. Haplotype frequencies, linkage disequilibrium, heterozygosity test and Hardy-Weinberg Equilibrium were estimated using ARLEQUIN software v.3.5. Results: Among all critically ill patients, an association between carriers of the +2960IN_+3142 G_+3187A haplotype and septic shock (P = 0.047) was observed. Septic patients who carried the +2