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. 2024 Oct 29;15(11):1388.
doi: 10.3390/genes15111388.

Gene Variant Frequencies of IDO1, IDO2, TDO, and KMO in Substance Use Disorder Cohorts

Lindsey Contella  1   2 , Christopher L Farrell  1 , Luigi Boccuto  1 , Alain Litwin  3   4   5 , Marion L Snyder  2
Affiliations

Gene Variant Frequencies of IDO1, IDO2, TDO, and KMO in Substance Use Disorder Cohorts

Lindsey Contella et al. Genes (Basel). .

Abstract

Background: Substance use disorder in the United States represents a complex and growing public health crisis, marked by increasing rates of overdose deaths and the misuse of prescription medications. There is a critical need for furthering the understanding of the molecular and genetic mechanisms that can lead to substance use disorder. Identifying significant variants in the kynurenine pathway could help identify therapeutic targets for intervention.

Methods: The All of Us cohort builder evaluated the frequency of variants of four genes, TDO2, IDO1, IDO2, and KMO, encoding enzymes in the kynurenine pathway. The samples were broken into six cohorts: alcohol, cannabis, cocaine, opioid, other use disorder, and control. Using Chi-square analysis, the frequency of at least one copy of a variant allele was calculated.

Results: Chi-square analysis showed a significant variation in genetic frequency (p-value < 0.005) in 14 of 18 polymorphisms analyzed. The cocaine cohort had the most significant variants (13), cannabis had 11, opioids had 3, other use disorders had 2, and alcohol had 1 significant variant.

Conclusions: This study found associations of polymorphisms in the TDO2, IDO1, IDO2, and KMO genes of individuals with a substance use disorder. These results provide evidence of potential predictors of increased susceptibility to substance use disorder.

Keywords: genetic frequency; kynurenine pathway; substance use disorder; tryptophan.

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Conflict of interest statement

Authors Contella, L. and Snyder, M.L were employed by the company Luxor Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Tryptophan metabolism through the kynurenine pathway. Abbreviations: IDO1: indoleamine 2,3-dioxygenase-1, IDO2: indoleamine 2,3-dioxygenase-2, TDO: tryptophan 2,3-dioxygenase, NAD+: nicotinamide adenine dinucleotide.
Figure 2
Figure 2
Study workflow and cohort definition for evaluating the frequency of genetic variants of the TDO2, IDO1/2 and KMO in substance use disorder.
See this image and copyright information in PMC

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