title: Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra-abdominal infection and/or pneumonia.
abstract: Sepsis is a leading cause of death around the world, and 73-83% of all sepsis cases requiring attention in intensive care units are linked to intra-abdominal infection (IAI) or pneumonia. The activation of innate immunity is central to the manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role in this activation process. The 299G and 399I alleles of TLR4 have been linked with an increased risk of Gram-negative bacteria (GNB) infections and septic shock in some populations. This case-control study evaluated the prevalence of D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05-12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS), confirming the co-segregation of these alleles in this population. Furthermore, the patients with a GNB infection and severe sepsis were not carriers of the risk alleles. In summary, this report shows that the frequency of the D299G and T399I polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms among different populations. Consequently, this study was not able to detect associations between TLR4 polymorphisms and sepsis in this population.
authors.affiliation: Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. ca.rodriguezosorio@gmail.com
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rodriguez-Osorio
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.forename: Jaime O
authors.initials: JO
authors.lastname: Herrera-Caceres
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Villegas-Torres
authors.forename: Joaquin
authors.initials: J
authors.lastname: Zuñiga
authors.forename: Sergio
authors.initials: S
authors.lastname: Ponce-de-Leon
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
authors.forename: Jose
authors.initials: J
authors.lastname: Sifuentes-Osornio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005658:Fungi / Q000276:immunology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006090:Gram-Negative Bacteria / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology; D006801:Humans; D059413:Intraabdominal Infections / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D011014:Pneumonia / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D018805:Sepsis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: GNB; Gram-negative bacteria; HWE; Hardy–Weinberg equilibrium; IAI; INCMNSZ; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran; LPS; Mestizo; Mexico; PAMP; Polymorphism; SNP; STR; Sepsis; TLR; TLR4; dbSNP; intra-abdominal infection; lipopolysaccharide; pathogen-associated molecular patterns; short tandem repeats; single nucleotide polymorphism; single nucleotide polymorphism database; toll-like receptor