Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: Gender-specific genetic predisposition to sepsis

Objectives: To determine whether the genotype frequencies of the five bi-al lelic polymorphisms in the bactericidal/permeability increasing protein (BP I) (Lys(216) --> Glu; Pstl polymorphism in intron 5; silent mutation G(545) --> C) and the lipopolysaccharide binding protein (LBP) (Cys(98) --> Gly; Pro(436) --> Leu) are associated with the incidence and lethality of sepsis . Design: Gase control study of patients with sepsis. Setting: Intensive care units within university hospitals. Patients: A total of 204 patients diagnosed with sepsis and 250 healthy blo od donors. Interventions: None. Measurements and Main Results:Short DNA fragments containing the polymorphi c sites of the LBP and BPI locus were amplified by the polymerase chain rea ction or mismatched polymerase chain reaction. The individual polymorphisms were determined with the appropriate restriction enzyme digestions and sub sequent agarose gel electrophoresis. The presence of LBP genotypes with the less frequent Gly(98) allele was found to be associated with sepsis (p < . 02) in male patients, but not in females. Patients which were homozygote fo r either of the rare Gly(98) (n = 6) and/or Leu(436) (n = 5) LBP alleles, f urthermore, exclusively were nonsurvivors of sepsis. The genotype frequenci es in the BPI gene did not differ between patients and control individuals. Conclusions: Our findings suggest that common polymorphisms in the gene for LBP in combination with mate gender are associated with an increased risk for the development of sepsis and, furthermore, may be linked to an unfavor able outcome. These data support the important immunomodulatory role of LBP in Gram-negative sepsis and suggest that genetic testing may be helpful fo r the identification of patients with an unfavorable response to Gram-negat ive infection.