Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis

doi:10.5847/wjem.j.issn.1920-8642.2012.02.008

Abstract

Abstract:

BACKGROUND: The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved. However, few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk. This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.

METHODS: In this case-control study, 192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192 healthy volunteers were enrolled. Exclusion criteria included metastatic tumors, autoimmune diseases, AIDS or treatment with immunosuppressive drugs. This study was approved by the ethical committee of Zhongshan Hospital, Fudan University. Sepsis patients were divided into a survival group (n=124) and a non-survival group (n=68) according to the 30-day mortality. Primer 3 software was used to design PCR and sequencing primers. Genomic DNA was extracted from peripheral blood mononuclear cells. Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing. The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.

RESULTS: The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium. The allele and genotype frequencies of rs4251545 (G/A) were significantly different between the severe sepsis and healthy control groups (P=0.015, P=0.035, respectively). Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G (OR=1.69, 95% CI: 1.10-2.58). The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.

CONCLUSION: These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.

Key words: Severe sepsis, IRAK-4, Single nucleotide polymorphism, Susceptibility, Prognosis, Chinese Han population, Allele, Genotype

Jun Yin, Yao Chen-ling, Cheng-long Liu, Zhen-ju Song, Chao-yang Tong, Pei-zhi Huang. Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis[J]. World Journal of Emergency Medicine, 2012, 3(2): 123-127.

Figures/Tables 3

Table 1

Table 2

Table 3

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Variables	Survivors (n=124)	Non-survivors (n=68)	P value
Age (years)	63.5±11.4	67.16±13.02	> 0.05
Males/Females	75 / 49	39 / 29	> 0.05
APACHE II	12.75±1.03	18.55±1.42	< 0.05
Length of hospital stay (days)	11.6	19.60	< 0.05

Variables	Healthy controls	Patients with sepsis	Allelic		Genotypic
Variables	Healthy controls	Patients with sepsis	P	OR	P
rs4251533			0.460	1.14 (0. 80-1.64)	0.587
AA	127	123
AG	58	58
GG	6	10
rs4251481			0.303	1.31 (0.79-2.17)	0.487
AA	165	160
AG	25	27
GG	2	5
rs4251545			0.015	1.69 (1.10-2.58)	0.035
GG	154	139
AG	36	43
AA	2	10
rs4238087			0.190	0.75 (0.49-1.15)	0.287
AA	140	149
AG	46	40
GG	4	1
rs4251431			0.182	0.74 (0.48-1.15)	0.283
GG	140	151
GT	50	40
TT	1	0
rs1461567			0.162	1.23 (0.92-1.64)	0.286
CC	60	50
CT	108	109
TT	21	30
rs4251513
CC	58	62	0.823	0.97 (0.77-1.30)	0.872
CG	114	109
GG	17	18

Variables	Survivors	Non- survivors	Allelic		Genotypic
Variables	Survivors	Non- survivors	P	OR	P
rs4251533			0.217	1.38 (0.83-2.30)	0.055
AA	81	42
AG	40	18
GG	3	7
rs4251481			0.295	1.44 (0.73-2.87)	0.130
AA	107	53
AG	13	14
GG	4	1
rs4251545			0.928	0.97 (0.55-1.72)	0.059
GG	87	52
AG	33	10
AA	4	6
rs4238087			0.346	0.71 (0.35-1.45)	0.145
AA	94	55
AG	30	10
GG	0	1
rs4251431			0.444	1.30 (0.66-2.54)	0.457
GG	101	50
GT	24	16
TT	0	0
rs1461567			0.053	1.52 (0.99-2.33)	0.052
CC	36	14
CT	74	35
TT	14	16
rs4251513			0.724	1.08 (0.70-1.67)	0.765
CC	20	42
CG	41	68
GG	6	12

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