10.6084/m9.figshare.5267791.v1 Sampath V. Sampath V. Mulrooney N. Mulrooney N. Patel A.L. Patel A.L. Cohen J. Cohen J. Zhang L. Zhang L. Garland J. Garland J. Lavoie P.M. Lavoie P.M. Dagle J. Dagle J. Simpson P. Simpson P. Supplementary Material for: A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants Karger Publishers 2017 NOD1 SNP Premature infants Blood culture sepsis NOD-like receptor variants Genetic susceptibility 2017-08-02 12:16:52 Journal contribution https://karger.figshare.com/articles/journal_contribution/Supplementary_Material_for_A_Potential_Role_for_the_NOD1_Variant_rs6958571_in_Gram-Positive_Blood_Stream_Infection_in_ELBW_Infants/5267791 <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>