Year: 2024
Type: conference-paper
Abstract: Background Acute intermittent porphyria (AIP) is a rare inherited metabolic disorder characterized by neurological manifestations, including abdominal pain. Identifying new biomarkers is crucial for improving the diagnosis and monitoring of AIP. We sequenced blood mRNA from 12 individuals, comprising six symptomatic AIP patients and six matched controls, to identify differentially expressed genes between the two groups.Methods StarSeq (Mainz, Germany) performed total RNA sequencing using the Illumina NextSeq 500™ platform on samples from 12 individuals, comprising six matched controls and six symptomatic AIP patients. Participants were chosen from a case-control study that included 50 AIP cases and 50 controls matched for gender, age, and place of residence. The six AIP cases, three women and three men, aged 20–75 years—were selected based on currently elevated urine porphobilinogen (PBG)/creatinine levels and having had AIP attacks. Differential mRNA expression analysis was conducted using the R package edgeR (version 3.42.4). Plasma cytokines and several diabetogenic hormones were measured using multiplex technology. Urine PBG and plasma kidney and liver function tests were conducted using routine methods. Results were compared with the Wilcoxon matched-pairs signed rank test.Results EdgeR analysis showed that C-type lectin domain family member 10A (CLEC10A) mRNA was differentially expressed in the 6 AIP cases compared to matched controls (log fold-change = 1.05, p = 2.09E-06, adj. p = 0.0519). No other significant mRNA expressions were found. As anticipated, the 6 AIP cases had significantly elevated porphyrin PBG/creatinine levels in urine compared to the 6 matched controls. Additionally, they had significantly elevated levels of 23 different cytokines and growth factors in plasma compared to their matched controls (p < 0.05). The selected AIP cases and their matched controls did not have diabetes. No significant differences were observed in S-glucose, B-HbA1c, P-C-peptide, P-insulin, S-ALT, S-Creatinine, or BMI between cases and controls (all p > 0.05). These results highlight CLEC10A’s potential as a biomarker for diagnosing and monitoring AIP-related inflammation.Conclusion CLEC10A mRNA was significantly upregulated (p-value = 2.09E-06) in symptomatic AIP compared to matched controls, although the adjusted p-value (adj.p.val = 0.0519) was on the boundary of statistical significance. Hence, further qPCR and ELISA analyses are underway to verify CLEC10A as a potential AIP biomarker.CLEC10A is linked to glucose metabolism and inflammation; supporting the hypothesis that differences in these pathways may be associated with AIP disease activity. Our RNA dataset shows no significantly increased cytokine mRNA in blood samples, suggesting that the elevated plasma cytokines in AIP come from organ damage, e.g. in liver or kidneys, and not from blood leukocytes.
Institutions: Nordland Hospital Trust, UiT The Arctic University of Norway
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402696287