Faculty Collaboration Database

A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants. Neonatology 2017;112(4):354-358

Date

08/03/2017

Pubmed ID

28768269

DOI

10.1159/000477433

Scopus ID

2-s2.0-85026855801 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

BACKGROUND: The genetic basis of sepsis susceptibility in preterm infants remains understudied. Herein, we investigated the nucleotide binding-oligomerization domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for preterm sepsis susceptibility.

OBJECTIVE: To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants.

METHODS: An international cohort of infants with gestational age (GA) <35 weeks were genotyped for SNPs in the ATG16L1, CARD8, NLRP3, NOD2, and NOD1 genes. χ2 and logistic regression analyses were used to examine relationships between NLR variants and BSI.

RESULTS: Among 764 infants, 138 developed BSI, 113 had gram-positive bacterial (GPB) BSI, and 28 had gram-negative bacterial (GNB) BSI. Infants with BSI had a lower birth weight and GA (p < 0.001), but did not differ in gender, race, or chorioamnionitis. NLR variants were not associated with GPB or GNB BSI in the entire cohort. The CC genotype of the NOD1 SNP (rs6958571) was associated with increased GPB BSI in extremely low birth weight (ELBW, birth weight <1,000 g) infants (OR = 3.3, 95% CI: 1.4-7.5, p = 0.003, n = 362) and in Caucasian infants (OR = 2.5, 95% CI: 1.2-5.4, p = 0.016, n = 535). Regression models adjusting for clinical variables identified ELBW status and the NOD1 CC genotype as risk factors for GPB BSI in Caucasian infants.

CONCLUSIONS: In this study investigating relationships between NLR variants and sepsis in infants with GA <35 weeks, the NOD1 (rs6958571) SNP was associated with GPB BSI in Caucasian infants and ELBW infants. Replication of our results in an independent cohort would support a role for NLR variants in determining sepsis risk in ELBW infants.

Author List

Sampath V, Mulrooney N, Patel AL, Cohen J, Zhang L, Garland J, Lavoie PM, Dagle J, Simpson P

Author

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Bacteremia
Birth Weight
Chi-Square Distribution
Female
Gene Frequency
Genetic Predisposition to Disease
Gestational Age
Gram-Positive Bacterial Infections
Humans
Infant, Extremely Low Birth Weight
Infant, Newborn
Infant, Premature
Logistic Models
Male
Nod1 Signaling Adaptor Protein
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide
Risk Factors