CD14 C(-260)T启动子多态性对冠心病患者C反应蛋白水平的影响

目的 探讨位于CD14基因启动子区域的C260T多态等位基因变异体CD14启动子区域-260位点C、T等位基因[CD14C(-260)T]启动子多态性对冠心病患者C反应蛋白水平的影响.方法 通过研究82例稳定性冠心病患者的高敏C反应蛋白(hs-CRP)水平检测组织炎症.结果 CD14基因中C260T多态性基因型分布如下:CC 18例(22%)、TC 48例(58.5%)、TT 16例(19.5%).相比于其它等位基因携带者TT型个体具有较高的hs-CRP(P=0.04).具有较高百分比的T等位基因纯合子其hs-CRP＞0.3mg/dl(P=0.01).结论 功能多态性的T纯合子在缺血性危险中是增高的,与hs-CRP＞0.3mg/dl是独立相关的(P=0.004).     

CD14C（-260）T启动子多态性对冠心病患者C反应蛋白水平的影响

目的探讨位于CD14基因启动子区域的C260T多态等位基因变异体CD14启动子区域-260位点C、T等位基因[CD14C(-260)T]启动子多态性对冠心病患者C反应蛋白水平的影响。方法通过研究82例稳定性冠心病患者的高敏C反应蛋白(hs-CRP)水平检测组织炎症。结果CD14基因中C260T多态性基因型分布如下:CC18例(22%)、TC48例(58.5%)、TT16例(19.5%)。相比于其它等位基因携带者TT型个体具有较高的hs-CRP(P=0.04)。具有较高百分比的T等位基因纯合子其hs-CRP>0.3mg/dl(P=0.01)。结论功能多态性的T纯合子在缺血性危险中是增高的,与hs-CRP>0.3mg/dl是独立相关的(P=0.004)。     

胱硫醚β合成酶基因多态性与脑卒中相关性的研究

目的　研究胱硫醚β合成酶 (CBS)基因 T2 7796 C多态性与脑卒中的遗传相关性。方法　采用限制性内切酶片段长度多态性方法 (PCR RFL P) ,对 5 9例脑卒中患者和 6 5例健康人 CBS基因 T2 7796 C多态性位点进行检测。结果　病例组 C等位基因占 5 6 .8% ,T等位基因占 4 3.2 % ;正常对照组 C等位基因占 5 1.5 % ,T等位基因占 4 8.5 % ;CBS基因 T2 7796 C多态性位点与脑卒中无明显相关 (P>0 .0 5 )。脑卒中组与正常对照组之间 3种等位基因型分布频率亦均无明显差异 ,其中 CC为 35 .6 %比 2 4 .6 % ;CT为 4 2 .4 %比 5 3.8% ;TT为2 2 .0 %比 2 1.5 % ;P>0 .0 5。缺血性卒中和出血性卒中组间 C、T等位基因及 3种等位基因型分布频率也均无显著性差异 (P均 >0 .0 5 )。结论　 CBS基因 T2 7796 C多态性位点与脑卒中无明显相关 ;T2 7796 C多态性位点与脑卒中的类型 (缺血性或出血性 )也无明显相关。     

ACE基因及CD14/-159基因多态性与变应性鼻炎关系的研究

目的通过对血管紧张素转换酶(angiotensin converting enzyme,ACE)基因插入/缺失的多态性及CD14/-159基因多态性分析,探讨其在变应性鼻炎(allergic rhinitis,AR)发病中的作用。方法采用PCR扩增及多聚酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)分析方法测定60例AR患者、40例健康体检者的ACE和CD14/-159基因型的分布情况,并对结果进行统计分析。结果ACE等位基因I、D频率在AR组和健康对照组间的分布具有显著性差异(X~2=17.37,P<0.005),等位基因D与AR的易感性相关(OR=3.46,95%CI=1.92～6.23,P<0.005)。CD14/-159等位基因C、T频率在AR组和健康对照组间的分布具有显著性差异(X~2= 14.53,P<0.005),等位基因C与AR的易感性相关(OR=3.1,95%CI=1.75～5.47,P<0.005)。两组ACE基因型(II、ID、DD)频率的分布比较有显著性差异(X~2=15.41,P<0.005);两组CD14/-159基因型(CC、CT、TT)频率的分布比较具有显著性差异(X~2=11.77,P<0.005)。结论ACE基因多态性与CD14/-159基因的多态性是影响AR的重要候选基因,其中以DD、ID、CC基因型和D、C等位基因与AR的易感性相关。     

精神分裂症患者MDR1多态性与帕利哌酮血药浓度相关性研究

目的通过测定精神分裂症患者使用帕利哌酮治疗期间其血药浓度变化及患者多药耐药1(MDR1)C3435T的基因多态性,探讨血药浓度与MDR1C3435T基因型之间的关系。方法采用液相色谱-串联质谱法,于帕利哌酮口服治疗后1周末、2周末、4周末及6周末监测61例精神分裂症患者血药浓度,同时在治疗6周末采用LDR-PCR方法测定MDR1C3435T基因型,对不同基因型及不同等位基因患者帕利哌酮血药浓度进行比较分析。结果 61例精神分裂患者中,CC、CT、TT所占比例分别为24.59%(15/61)、63.30%(38/61)、13.11%(8/61),其中CT杂合子所占比例明显高于CC和TT纯合子(P0.05),C等位基因与T等位基因所占比例分别为55.74%和44.26%(P0.05)。4个检测时间点TT基因型药物浓度均明显高于CC基因型,仅在第1周末TT基因型血药浓度明显高于CT基因型,CT基因型高于CC基因型(P0.05)。4个检测时间点带T等位基因患者的帕利哌酮血药浓度均高于C等位基因患者,但仅第1周末差异具有统计学意义(P0.05)。结论精神分裂症患者MDR1C3435T基因多态性与帕利哌酮的药物浓度具有一定的相关性。     

亚甲基四氢叶酸还原酶基因SNP677C/T 与肺癌易感性关系的研究

目的 研究亚甲基四氢叶酸还原酶(MTHFR)基因多态性与肺癌易感性的关系.方法 本研究选取120 例宣威地区女性肺癌患者为病例组,60 例宣威地区女性肺良性病变患者为对照组.采用多聚酶链式反应-限制性片段长度多态性方法检测MTHFR 基因SNP677C/T 在病例组和对照组中的分布,探讨SNP677C/T 位点与肺癌易感性的关系.结果 (1)MTHFR 基因SNP677C/T等位基因频率和基因型频率在肺癌患者和对照组中的分布有统计学差异(P ＜0.001 和P ＝0.002);(2)SNP677C/T的T 等位基因可增加肺癌的患病风险(OR ＝2.330,95% CI:1.489 ～3.646 );(3)MTHFR基因SNP677C/T 的等位基因频率和基因型频率分布在不同病理类型的肺癌患者中无统计学差异(P ＝0.814 和P ＝0.860).结论 MTHFR 基因SNP677C/T 变异与宣威地区女性肺癌的发生相关.     

白细胞介素-18基因多态性与肺结核病易感性的关系

目的：通过病例-对照研究,探讨白细胞介素-18（IL-18）基因启动子区-607C/A、-137G/C位点单核苷酸多态性（SNP）与肺结核病的关系。方法：采用序列特异性引物PCR（PCR-SSP）及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例IL-18启动子区-607 C/A 、-137G/C位点多态性基因型。采用直接计数法计算各组基因型频率及等位基因频率,进行χ2 检验。以P值＜0.05为具有统计学意义。结果：肺结核患者IL-18启动子区-607位点A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为19.5%、55.0%、25.5% ;A、C等位基因频率分别为47.0%、53.0%。健康对照者A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为22.8%、46.7%、30.5%;A、C等位基因频率分别为46.2%、53.8%。两组人群-607位点基因型及等位基因分布无明显差异(P>0.05)。肺结核患者IL-18启动子区-137G/C位点C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为4.5%、18.5%、77.0%;C、G等位基因频率分别为13.8%、86.2%。健康对照者C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为5.6%、25.9%、68.5%;C、G等位基因频率分别为18.5%、81.5%。两组人群-137位点基因型分布无明显差异(P>0.05)。结论：IL-18启动子区-607、-137位点基因多态性与中国汉族人群肺结核病易感性无关。     

MMP-9基因多态性与儿童呼吸道合胞病毒毛细支气管炎易感性及严重程度相关性研究

目的：探讨MMP-9基因-1562和R279Q位点多态性与儿童呼吸道合胞病毒（respiratory syncytial virus,RSV）毛细支气管炎易感性及严重程度之间的关系。方法对RSV感染致毛细支气管炎患儿142例（实验组）和健康儿童80例（对照组）,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法,检测MMP-9基因-1562和R279Q位点多态性基因型,比较不同位点不同基因型与毛细支气管炎易感性及严重程度之间的关系。结果 MMP-9基因-1562位点存在3个基因型,即C/C、C/T、T/T,分布频率分别为72.54%、26.01%、1.41%;MMP-9基因R279Q位点存在3个基因型,即C/C、C/G、G/G,分布频率分别为58.45%、33.80%、7.75%。MMP-9基因-1562位点不同基因型之间,毛细支气管炎严重程度差异有统计学意义（P〈0.05）。MMP-9-1562位点的C/T基因型携带者比C/C基因型携带者更容易发生毛细支气管炎,风险上升2.25倍（95%C. I.：1.08~4.72）;MMP-9 R279Q位点的C/C基因型携带者更容易发生毛细支气管炎,风险上升1.90倍（95%C.I.：1.03~3.58）。结论 MMP-9基因-1562和R279Q位点多态性基因型与RSV毛细支气管炎易感性相关,而-1562位点多态性与其严重程度相关。     

白介素10基因多态性与术后脓毒症发生发展的相关研究

目的研究白介素10（IL-10）基因启动子区域中IL-10-592、IL-10-819、IL-101-082基因多态性与术后严重脓毒症易感性及其预后的相关性。方法采用聚合酶链反应（PCR）结合RsaⅠ、MaeⅢ、MnlⅠ限制性内切酶酶切分析法检测116例术后并发严重脓毒症患者和141例健康献血员（对照组）的IL-10-592、IL-10-819、IL-10-1082基因多态性。结果IL-10-1082等位基因1的频率在脓毒症组为59.9％,对照组为50.4%（P<0.05）;IL-10-1082基因型分布频率在脓毒症组和对照组间有显著性差异（P<0.05）;而IL-10-592、IL-10-819等位基因频率及基因型频率在脓毒症组和对照组间均无显著性差异（P均>0.05）;IL-10-592、IL-10-819、IL-10-1082等位基因频率及基因型频率在死亡的与存活的脓毒症患者间均无显著性差异（P均>0.05）。结论IL-10-1082基因多态性与术后严重脓毒症的易感性有关,与其预后不相关;而IL-10-592、IL-10-819基因多态性与术后严重脓毒症的易感性及预后均不相关。     

中国南方汉族人群不稳定性心绞痛患者基质金属蛋白酶9基因C1562T多态性的特点

目的:了解基质金属蛋白酶9基因C1562T多态性与中国南方汉族人群不稳定型心绞痛易感性的关系。方法:选择2003-06/2006-06湘南学院附属医院对经冠状动脉造影证实的不稳定型心绞痛患者90例(不稳定型心绞痛组)和同期冠状动脉造影阴性、排除冠心病诊断的患者70例(对照组)。采用酶联免疫吸附试验测定血浆基质金属蛋白酶9水平,采用多聚酶链反应-限制性内切酶片断长度多态性技术分析基质金属蛋白酶9基因中C1562T基因多态性,比较各组的基因型和等位基因频率。结果:所有受试者完成测试并进入结果分析,无脱落者,DNA抽提均成功。①不稳定型心绞痛组血浆基质金属蛋白酶9水平明显高于对照组[(108.65±32.54),(51.12±12.47)μg/L](P<0.01)。②不稳定型心绞痛组基质金属蛋白酶9基因CT基因型频率(28%)以及T等位基因频率(16.1%)均高于对照组(16%,9.3%),差异有显著性(P<0.05)。③C1562T位点CT/TT基因型患者血浆基质金属蛋白酶9水平高于CC基因型患者[(92.12±39.56),(73.46±28.67)μg/L](P<0.05)。结论:基质金属蛋白酶9基因C1562T多态性与中国南方汉族人群不稳定型心绞痛有关,1562T等位基因可能是不稳定型心绞痛遗传易感性的基因标记之一。     

The –260 C→T promoter polymorphism of the lipopolysaccharide receptor CD14 and severe sepsis in trauma patients

OBJECTIVE: CD14, expressed on the cell surface of monocytes and hepatic Kupffer cells, interacts with Gram-positive and Gram-negative bacteria. Upon CD14 stimulation, these cells respond with the enhanced release of cytokines involved in the pathophysiology of sepsis. The purpose of this study was to evaluate whether the genotype distribution of the -260 C-->T promoter polymorphism of the CD14 gene is associated with the development of severe sepsis in trauma patients. PATIENTS AND PARTICIPANTS: Fifty-eight severely injured blunt trauma patients with an injury severity score of 16 or more and without pre-existing chronic diseases. MEASUREMENTS AND RESULTS: Genotyping for the single nucleotide exchange polymorphism of the CD14 gene was performed by means of a real-time polymerase chain reaction with fluorescence-labeled hybridization probes. Diagnosis of severe sepsis was based on the criteria of the ACCP/SCCM criteria. Fourteen out of the 58 patients (24.6%) developed a trauma-related severe sepsis. The overall allele frequency was 0.58 for the C allele and 0.42 for the T allele. The genotype distribution (TT 0.19, CT 0.47 and CC 0.35) did not differ significantly from a previously reported control group of healthy blood donors. There was no significant difference of the genotype distribution or allele frequency between trauma patients with severe sepsis and patients with an uncomplicated clinical course. CONCLUSIONS: This pilot study suggests that the CD14 -260 polymorphism is not associated with an increased risk of severe sepsis in trauma patients.     

Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate

OBJECTIVE: Genetic differences in immune responses may affect susceptibility to and outcome of septic shock. CD14 seems to be an important part of the innate immune system, initiating antimicrobial response. We evaluated the frequency of a recently discovered CD14 promoter gene polymorphism (C to T transition at base pair -159) among patients with septic shock compared with those in a control group. DESIGN: Multiple-center study. SETTING: Hospital research department. PATIENTS: Ninety consecutive white patients with septic shock were included. The control group consisted of 122 age- and gender-matched white subjects. INTERVENTIONS: In both groups, the C-159T CD14 promoter genetic polymorphism was determined by using polymerase chain reaction and subsequent Hae III restriction enzyme digestion of the polymerase chain reaction products. MEASUREMENTS AND MAIN RESULTS: The C-159T polymorphism and the TT genotype were significantly overrepresented among septic shock patients compared with controls. Within the septic shock group, the mortality of patients with TT genotype (71%) was significantly higher than in patients with other genotypes (48%; Pearson chi-square, p =.008). In a multiple logistic regression model, the TT genotype was independently associated with an increased relative risk of death (odds ratio, 5.30; 95% confidence interval, 1.20-22.50, p =.02). CONCLUSIONS: The C-159T polymorphism affects susceptibility to septic shock and seems to be a new genetic risk factor for death.     

Effects of CD14-159 C/T polymorphism on CD14 expression and the balance between proinflammatory and anti-inflammatory cytokines in whole blood culture

CD14 is an important receptor of innate immunity. When CD14 is anchored by ligands to LPS, peptidoglycans, or lipoteichoic acid, it can result in either proinflammatory or anti-inflammatory responses. To determine whether CD14-159 C/T polymorphism is associated with CD14 expression and the balance of proinflammatory and anti-inflammatory responses, we studied 118 healthy ethnic Han Chinese using a whole blood culture model. The CD14-159 C/T polymorphism was determined by polymerase chain reaction and subsequent HaeIII restriction enzyme digestion of the polymerase chain reaction products. Meanwhile, CD14 mRNA expression in leukocytes and the levels of soluble CD14, TNF-alpha, IL-6, and IL-10 were also determined in the supernatants. Among the 118 individuals, there were 40 TT homozygotes, 62 heterozygotes, and 16 subjects homozygous for C allele. After LPS stimulation, the levels of CD14 mRNA expression in TT and TC genotypes were significantly higher than in CC homozygotes (P = 0.017), and soluble CD14 levels were also higher than in CC genotypes (P = 0.008). In addition, TT homozygotes had the highest LPS-stimulated TNF-alpha, IL-6 production (P = 0.044, P = 0.004), and the lowest IL-10 release (P = 0.003). In conclusion, CD14-159 C/T polymorphism is correlated with CD14 expression and may thus influence the balance of proinflammatory and anti-inflammatory responses in ethnic Han Chinese. These results suggest that CD14-159 C/T polymorphism might partly explain the difference in predisposition to develop complications of infectious diseases in different patients and may provide a therapeutic target for sepsis intervention strategies.     

分化抗原簇14基因多态性与感染易感性的相关研究

目的 通过检测分化抗原簇14基因（CD14）单核苷酸多态性（SNP）的频率分布．探讨基因多态性与感染易感性之间的关系。方法选择2004年12月-2006年3月进入重症加强治疗病房（ICU）并发全身性感染的患者112例，并以100名健康自愿献血者为正常对照组。采用聚合酶链反应（PCR）扩增限制性内切酶长度多态性（RFLP）的方法检测CD14基因上-159C／T及-260C／T两个位点的SNP。结果全身性感染组与正常对照组比较：两组CD14-159基因型分布差异有显著性（P=0．005），全身性感染组CD14-159的T等位基因出现频率显著高于正常对照组（P=0．000）；两组CD14-260基因型分布及等位基因出现频率差异均无显著性（P=0．912和P=0．706）。死亡组与存活组比较：两组CD14-159基因型分布差异有显著性（P=0．000），死亡组CD14-159的T等位基因出现频率显著高于存活组（P=0．000）；CD14-260基因型分布及等位基因出现频率在两组问差异均无显著性（P=0．643和P=0．890）。结论CD14基因-159C／TSNP的差异可能与全身性感染患者易感性及感染后病死率增高有关。     

Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis.

OBJECTIVE: To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism. DESIGN: Consecutive entry study of patients with severe sepsis. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Eighty-seven patients with a diagnosis of severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. CONCLUSIONS: Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.     

A Genetic Variant of the CD14 C-159T in Patients with Functional Dyspepsia (FD) in Japanese Subjects

Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. CD14 is an important mediator of the inflammatory response in the first line of host defense by recognition of Lipopolysaccharide (LPS). We aimed to investigate the association between CD14 promoter C-159T polymorphism and FD in a Japanese population. 108 patients with FD and 99 non-dyspeptic subjects enrolled in this study. Dyspeptic symptoms were divided according to Rome III criteria. CD14 gene C-159T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. In the non-dyspeptics, the CD14 genotype distribution was 28CC (28.3%), 51CT (51.5%), 21TT (21.2%). Meanwhile, the CD14 genotype distribution in FD was 31CC (28.4%), 56CT (51.4%), 22TT (20.2%). The genotype distribution was not significantly different. There was no significant difference between two groups in the genotype distribution. We did not found any association between CD14 genotypes and dyspeptic patients in different gender and Helicobacter pylori infection status. No significant association was also found between CD14 polymorphism and any of different subtypes of FD according to Rome III while there was a weak correlation between TT genotype and PDS in male subjects (TT vs others, OR = 3.18, 95% CI = 0.98-10.26, p = 0.06). In conclusion, our results suggest that CD14 polymorphism is unlikely to associate with susceptibility of dyspeptic symptoms. The role of inflammation related-gene polymorphisms to the development of dyspepsia needs to further evaluation.     

Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis.

OBJECTIVES: To determine whether the allele frequencies and genotype distribution of an interleukin (IL)-1beta TaqI polymorphism and an interleukin-1 receptor antagonist polymorphism are associated with susceptibility to and outcome of severe sepsis. In addition, we analyze a possible linkage disequilibrium between a previously described NcoI polymorphism within the tumor necrosis factor (TNF) locus and the two IL-1 gene family polymorphisms. DESIGN: Prospective, consecutive entry study of patients with diagnosis of severe sepsis. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Ninety-three patients with diagnosis of severe sepsis admitted to the ICU between June 1993 and June 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The polymorphic region within intron 2 of the IL-1ra gene containing variable numbers of a tandem repeat of 86 base pairs was amplified by means of the polymerase chain reaction. Alleles A1-5 are identified according to the size of the amplified DNA product. The region that contains the biallelic TaqI site within exon 5 of the IL-1beta gene was analyzed by polymerase chain reaction amplification and subsequent digestion using the TaqI restriction enzyme. A NcoI TNF-beta polymorphism was determined. The allele frequency of the allele IL-1raA2 was increased in 93 patients with severe sepsis compared with normal individuals (p < .01). No association with patients' outcome was observed. Allele frequencies or genotype distribution of the IL-1beta TaqI polymorphism did not differ between patients and controls. In addition, the allele TNFB2 of the NcoI TNF-beta polymorphism was associated with nonsurvival. Occurrence of the TNFB1 and TNFB2 alleles and genotypes was unrelated to alleles and genotypes of the two IL-1 gene family polymorphisms. CONCLUSION: In contrast to the TNF-beta NcoI polymorphism, which has been associated with patients' nonsurvival, the allele IL-1raA2 of the polymorphism within the intron 2 of IL-1ra may contribute to susceptibility to sepsis.     

Innate immunity SNPs are associated with risk for severe sepsis after burn injury

OBJECTIVE: To analyze allelic association with clinical outcome in a cohort of burn patients. PATIENTS: Two hundred twenty-eight individuals with burns > or =15% total body surface area without significant non-burn related trauma who survived >48 hours post-admission were enrolled. One hundred fifty-nine of these patients were analyzed previously. METHODS: Candidate polymorphisms within interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), cellular differentiation marker 14 (CD14) and toll-like receptor 4 (TLR4) were evaluated by logistic regression analysis for association with increased risk for severe sepsis (sepsis plus organ dysfunction or shock). RESULTS: After adjustment for age, burn size, ethnicity, gender and inhalation injury, alleles at TNF-alpha (308G, p=0.013), TLR4 (+896G, p=0.027), IL-6 (174C, p=0.040) and CD14 (159C, p=0.047) were significantly associated with an increased risk for severe sepsis. CONCLUSIONS: Carriage of variant alleles at immune response genes were associated with increased risk for severe sepsis after burn injury.