The genetic variant SLC2A1-rs1105297 is associated with the differential analgesic response to a glucose-based treatment in newborns

TL;DR

A genetic variant in the SLC2A1 gene is linked to how well newborns respond to glucose-based pain relief, suggesting personalized treatment could improve outcomes.

Contribution

Identifies a specific SLC2A1 genetic variant associated with differential analgesic response to glucose in newborns.

Findings

The G allele of SLC2A1-rs1105297 is linked to a fourfold decreased probability of responding to 33% glucose analgesia.

The variant decreases SLC2A1-AS1 expression, upregulating SLC2A1 in the dorsal striatum, which may affect opioid receptor binding.

Host genetics, particularly SLC2A1 variability, play a significant role in neonatal analgesic efficacy.

Abstract

Supplemental Digital Content is Available in the Text.

The genetic variability of SLC2A1 gene affects the neonatal response to a 33% glucose-based analgesic treatment, highlighting the importance of host genetics for personalized analgesia.

Neonatal pain is a critical issue in clinical practice. The oral administration of glucose-based solutions is currently one of the most common and effective nonpharmacologic strategies for neonatal pain relief in daily minor procedures. However, a varying degree of analgesic efficacy has been reported for this treatment. Environmental, maternal, and genetic factors may explain this variability and potentially allow for a personalized analgesic approach, maximizing therapeutic efficacy and preventing side effects. We investigated the exposome (ie, the set of clinical and anthropometric variables potentially affecting the response to the therapy) and the genetic variability of the noradrenaline transporter gene (solute carrier family 6 member 2 [SLC6A2]) and 2 glucose transporter genes (solute carrier family 2 member 1 [SLC2A1] and 2 [SLC2A2]) in relation to the neonatal analgesic efficacy of a 33% glucose solution. The study population consisted in a homogeneous sample of more than 1400 healthy term newborns. No association for the exposome was observed, whereas a statistically significant association between the G allele of SLC2A1-rs1105297 and a fourfold decreased probability of responding to the therapy was identified after multiple-testing correction (odds ratio of 3.98, 95% confidence interval 1.95-9.17; P = 4.05 × 10−4). This allele decreases the expression of SLC2A1-AS1, causing the upregulation of SLC2A1 in the dorsal striatum, which has been suggested to be involved in reward-related processes through the binding of opioids to the striatal mu-opioid receptors. Altogether, these results suggest the involvement of SLC2A1 in the analgesic process and highlight the importance of host genetics for defining personalized analgesic treatments.