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Polymorphic variants in exon 8 at the 3' UTR of the HLA-G gene are associated with septic shock in critically ill patients

Pietra Graebin12, Tiago D Veit1, Clarice S Alho2, Fernando S Dias3 and José AB Chies1*

Author Affiliations

1 Laboratory of Immunogenetics of Federal University of Rio Grande do Sul - 9500, Bento Gonçalves Av., Building 43323//Room 212, Porto Alegre, RS, Brazil

2 Laboratory of Human and Molecular Genetics of Pontifical Catholic University of Rio Grande do Sul, 6681, Ipiranga Av., Building 12C, Porto Alegre, RS, Brazil

3 São Lucas Hospital, Pontifical Catholic University of Rio Grande do Sul, 6681, Ipiranga Av., Building 12C, Porto Alegre, RS, Brazil

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Critical Care 2012, 16:R211  doi:10.1186/cc11845

Published: 29 October 2012

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 +2960IN_+3142G_+3187A haplotype presented an increased risk for septic shock (P = 0.031).

Conclusions

The present study showed, for the first time, an association between polymorphisms in exon 8 at the 3 'UTR of HLA-G gene and outcomes of critically ill patients. These results may be important for understanding the mechanisms involved in evolution to septic shock in critically ill patients.