Supplementary Material for: A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants

<p><b><i>Background:</i></b> 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. <b><i>Objective:</i></b> To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants. <b><i>Methods:</i></b> An international cohort of infants with gestational age (GA) <35 weeks were genotyped for SNPs in the <i>ATG16L1</i>, <i>CARD8</i>, <i>NLRP3</i>, <i>NOD2</i>, and <i>NOD1 </i>genes. χ<sup>2</sup> and logistic regression analyses were used to examine relationships between NLR variants and BSI. <b><i>Results:</i></b> 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 (<i>p</i> < 0.001), but did not differ in gender, race, or chorioamnionitis. <i>NLR</i> variants were not associated with GPB or GNB BSI in the entire cohort. The CC genotype of the NOD1 SNP <i>(</i>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, <i>p</i> = 0.003, <i>n</i> = 362) and in Caucasian infants (OR = 2.5, 95% CI: 1.2-5.4, <i>p</i> = 0.016, <i>n</i> = 535). Regression models adjusting for clinical variables identified ELBW status and the <i>NOD1</i> CC genotype as risk factors for GPB BSI in Caucasian infants. <b><i>Conclusions:</i></b> In this study investigating relationships between <i>NLR</i> variants and sepsis in infants with GA <35 weeks, the <i>NOD1 (</i>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.</p>