The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population.

Guoda Ma,Liangqing Zhang,Yiming Shao,Keshen Li,Yuliu Xie,Haiyang Wang,Guixi Mo,Hua Tao,Lili Cui,Bin Zhao,Xin Liu,Jiawu Fu,You Li,Jia Li

doi:10.1155/2014/701971

Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

Highlights

Sepsis is a clinical entity involving a massive systemic inflammatory response, which may result in septic shock, multiple organ system failure, and death [1]
These patients were diagnosed with sepsis, severe sepsis, or septic shock according to the 1991 ACCP/SCCM Joint Meeting [14] and the diagnostic criteria developed at the 2001 International Sepsis Definition Conference [15]
We investigated a common single-nucleotide polymorphism (SNP), Pro12Ala, in the Peroxisome proliferator-activated receptor-γ (PPAR-γ) gene in 308 patients with clinically defined sepsis and 345 age-matched healthy controls, and we evaluated the effects of this SNP on disease risk and progression

Summary

Introduction

Sepsis is a clinical entity involving a massive systemic inflammatory response, which may result in septic shock, multiple organ system failure, and death [1]. Peroxisome proliferatoractivated receptor gamma (PPAR-γ) was described as playing a role in modulating the pathological status of sepsis by regulating energy metabolism, inflammation, and immune cell function [2]. In animal models of sepsis and septic shock, PPAR-γ agonist pretreatment markedly attenuated inflammation compared with controls [6, 7]. PPAR-γ induces apoptosis, and the death of immune cells, especially T lymphocytes, is generally considered deleterious [2]. Under these circumstances, a second infection cannot be adequately cleared, leading to septic

Methods

Results

Conclusion