ArticleAlcoholism, clinical and experimental research2018
Genetic Association and Expression Analyses of the Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) Gene in Alcohol Use Disorder-Relevance for Pain Signaling and Alcohol Use.
Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Alcohol use disorder-associated pain: clinical and preclinical evidence.Alcohol (Fayetteville, N.Y.) · 2025Review
- Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies.Alcoholism, clinical and experimental research · 2020Review
- Novel genetic variants ofAmerican journal of cancer research · 2020Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe gene encoding phosphatidylinositol-4-phosphate 5-kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD.
methodsWe conducted a case-control association study of genetic variants in PIP5K1C. Association analyses of 16 common PIP5K1C single nucleotide polymorphisms (SNPs) were conducted in cases and controls of African (427 cases and 137 controls) and European ancestry (488 cases and 324 controls) using standard methods. In addition, given the prominent role of the opioid system in pain signaling, we investigated the effects of acute alcohol exposure on PIP5K1C expression in humanized transgenic mice for the μ-opioid receptor that included the OPRM1 A118G polymorphism, a widely used mouse model to study analgesic response to opioids in pain. PIP5K1C expression was measured in the thalamus and basolateral amygdala (BLA) in mice after short-term administration (single 2 g/kg dose) of alcohol or saline using immunohistochemistry and analyzed by 2-way analysis of variance.
resultsIn the case-control association study using an NIAAA discovery sample, 8 SNPs in PIP5K1C were significantly associated with AUD in the African ancestry (AA) group (p < 0.05 after correction; rs4807493, rs10405681, rs2074957, rs10432303, rs8109485, rs1476592, rs10419980, and rs4432372). However, a replication analysis using an independent sample (N = 3,801) found no significant associations after correction for multiple testing. In the humanized transgenic mouse model with the OPRM1 polymorphism, PIP5K1C expression was significantly different between alcohol and saline-treated mice, regardless of genotype, in both the thalamus (p < 0.05) and BLA (p < 0.01).
conclusionsOur discovery sample shows that genetic variants in PIP5K1C are associated with AUD in the AA group, and acute alcohol exposure leads to up-regulation of PIP5K1C, potentially explaining a mechanism underlying the increased risk for chronic pain conditions in individuals with AUD.
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