LBP rs2232618 polymorphism contributes to risk of sepsis after trauma

Abstract

BackgroundPrevious study revealed that rs2232618 polymorphism (Phe436Leu) within LBP gene is a functional variant and associated with susceptibility of sepsis in traumatic patients. Our aim was to confirm the reported association by enlarging the population sample size and perform a meta-analysis to find additional evidence.MethodsTraumatic patients from Southwest (n = 1296) and Southeast (n = 445) of China were enrolled in our study. After genotyping, the relationship between rs2232618 and the risk of sepsis was analyzed. Furthermore, we proceeded with a comprehensive literature search and meta-analysis to determine whether the rs2232618 polymorphism conferred susceptibility to sepsis.ResultsSignificance correlation was observed between rs2232618 and risk of sepsis in Southwest patients (P = 0.002 for the dominant model, P = 0.006 for the recessive model). The association was confirmed in Southeast cohort (P = 0.005 for the dominant model) and overall combined cohorts (P = 4.5 × 10−4, P = 0.041 for the dominant and recessive model). Multiple logistical regression analyses suggested that rs2232618 polymorphism was related to higher risk of sepsis (OR = 1.77, 95% CI = 1.26–2.48, P = 0.001 in Southwest patients; OR = 2.11, 95% CI = 1.24–3.58, P = 0.006 in Southeast cohort; OR = 1.54, 95% CI = 1.34–2.08, P = 0.006 in overall cohort). Furthermore, meta-analysis of four studies (including the present study) confirmed that rs2232618 within LBP increased the risk of sepsis (OR = 1.75, P < 0.001 for the dominant model; OR = 6.08, P = 0.003 for the recessive model; OR = 2.72, P < 0.001 for the allelic model).ConclusionsThe results from our replication study and meta-analysis provided firm evidence that rs2232618T allele significantly increased the risk of sepsis.

Effects of Lipopolysaccharide-Binding Protein (LBP) Single Nucleotide Polymorphism (SNP) in Infections, Inflammatory Diseases, Metabolic Disorders and Cancers

“…Furthermore, Leu436 LBP protein has stronger binding interactions with CD14 (p=0.043) ( 48 ). Lu and their groups confirmed the correlation between genotypic distributions and traumatic sepsis in an enlarged co-located population sample size with 1296 patients in Chongqing (TT vs. TC+CC, p=0.002 for sepsis morbidity rate and p=1.8E-6 for MOD scores, respectively) and 445 patients in Zhejiang (TT vs. TC+CC, p=0.002 for sepsis morbidity rate and p=0.005 for MOD scores, respectively) ( 50 ). Combined analysis of two cohorts also showed relevance between rs2232618 and traumatic sepsis (TT vs. TC+CC, p=4.5×10 -4 for sepsis morbidity rate and p=1.4E-9 for MOD scores, respectively) ( 50 ).…”

A Genetic Variation of Lipopolysaccharide Binding Protein Affects the Inflammatory Response and Is Associated with Improved Outcome during Sepsis

“…Therefore, no conclusive picture regarding risk alleles could be drawn from these data. Interestingly, the F436L SNP examined in this study was associated with a higher prevalence of sepsis in a cohort of trauma victims of Han Chinese origin with a different demographic composition (38,39).…”

“…Patients carrying this SNP were excluded from the primary analysis. The SNP further evaluated in this study has been shown by others to be associated with altered sepsis prevalence and mortality in Chinese trauma victims (38,39).…”