Role of Polymorphic Variants as Genetic Modulators of Infection in Neonatal Sepsis

Abstract

This study is a retrospective, case control study involving 535 preterm infants examining the roles of sequence polymorphisms in genes that mediate host immune responses to bacterial infection in newborn infants. A total of 49 single nucleotide polymorphisms (SNPs) in 19 candidate genes including inflammatory cytokines (IL6, IL10, IL1B, and TNF), cytokine receptors (IL1RN), toll-like receptors (TLR2, TLR4, and TLR5), and cell surface receptors (CD14) were genotyped. Subjects were stratified into three groups (sepsis, suspected sepsis, and control). The data were analyzed using a family-based transmission disequilibrium test. We found that birth weight, gestational age, duration of rupture of membranes, and presence of clinical chorioamnionitis were strongly associated with sepsis. Polymorphisms in TLR2 (rs3804099), TLR5 (rs5744105), IL10 (rs1800896), and PLA2G2A (rs1891320) genes were associated with sepsis. Allelic variants in PLA2G2A and TLR2 were associated with Gram-positive infections, whereas IL10 was associated with Gram-negative infections (p Ͻ 0.05). We conclude allelic variations in PLA2G2A, TLR2, TLR5, and IL10 may moderate the predisposition to sepsis in preterm infants. (Pediatr Res 68: 323-329, 2010)

Association of single nucleotide polymorphisms in pro-inflammatory cytokine and toll-like receptor genes with pediatric hematogenous osteomyelitis

“…The frequency of expression of the AA rs16944 (P = 0.005, Pc = 0.05) and A rs16944 (P = 0.0007, Pc = 0.007) alleles, on the other hand, were significantly higher in patients (approximately 4.2 and 2.3 times, respectively) than in controls, indicating this genotype and allele to be risk factors for this type of infection. Zheng et al (2013) suggested that G rs16944 is associated with an increased risk of esophageal squamous cell carcinoma, while a meta-analysis of studies analyzing individuals of European descent Abu-Maziad et al (2010) reported that osteomyelitis of the hand was associated with rs16944. However, Jotanovic et al (2012) did not identify a significant association between this SNP and osteoarthritis in Caucasian patients.…”

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

“…Moreover, associations between the TLR2 genetic diversity and Alzheimer's disease [61] or cognitive function in schizophrenia [62] are highly suggestive of genetically-driven inter-individual ability to modulate neuroinflammatory processes. Of importance is that the TLR2 rs3804099 polymorphism was showed on the one hand to be associated with several inflammatory and infectious diseases including pulmonary tuberculosis, neonatal infection, filariasis, ocular Behcet's disease and cancer [63][64][65][66][67] and to exert a functional impact on the inflammatory response on the other [65,68,69].…”

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective

“…Aydemir et al 21 Härtel et al 9 Abu-Maziad et al 22 Auriti et al 23 Koroglu et al 24 Spiegler et al 25 Abdel-Hady et al 26 Bertalan et al 27 Reiman et al 28 Dzwonek et al 29 van Der Zwet et al 30 Schueller et al 31 Derzbach et al 32 Härtel et al 33 Baier et al 34 Göpel et al…”

“…were genotyped. 22 The subjects were stratified into three groups There have been no instances in which a large cohort study was the first to identify a major effect on susceptibility to sepsis from any of the candidate genes, although strong effects on predisposing conditions such as premature birth 39 could be identified through this approach.…”