Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.
OBJECTIVE
Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.


METHODS
A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705), -764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated.


RESULTS
No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r(2) = 0.894). The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.


CONCLUSIONS
Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Ding
D
Wang
The department of intensive care unit, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xuan
X
Zhong
The department of intensive care unit, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Dongjian
D
Huang
Reproductive Department, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Rui
R
Chen
The department of intensive care unit, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guibin
G
Bai
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Qing
Q
Li
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Bolan
B
Yu
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Yong
Y
Fan
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xiaofang
X
Sun
D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018410:Pneumonia, Bacterial / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index
D007371:Interferon-gamma