Genetic variants in AKR1B10 associate with human eating behavior

Abstract

BackgroundThe human Aldoketoreductase 1B10 gene (AKR1B10) encodes one of the enzymes belonging to the family of aldoketoreductases and may be involved in detoxification of nutrients during digestion. Further, AKR1B10 mRNA (messenger ribonucleic acid) expression was diminished in brain regions potentially involved in the regulation of eating behavior in rats which are more sensitive to cocaine and alcohol. We hypothesized that the human AKR1B10 gene may also play a role in the regulation of human eating behavior.ResultsWe investigated the effects of 5 genetic variants of AKR1B10 on human eating behavior among 548 subjects from a German self-contained population, the Sorbs, and in 350 subjects from another independent German cohort. Among the Sorbs, we observed nominal associations with disinhibition at the 5′ untranslated region (5′ UTR) variant rs10232478 and the intragenic variants rs1834150 and rs782881 (all P ≤ 0.05). Further, we detected a relationship of rs1834150 and rs782881 with waist, smoking consumption (rs782881) and coffee consumption (rs1834150) (all P ≤ 0.05). Albeit non-significant, replication analyses revealed similar effect directions for disinhibition at rs1834150 (combined P = 0.0096). Moreover, in the replication cohort we found rs1834150 related to increased restraint scores with a similar direction as in the Sorbs (combined P = 0.0072).ConclusionOur data suggest that genetic variants in the AKR1B10 locus may influence human eating behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0189-9) contains supplementary material, which is available to authorized users.

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“…Candidate gene and gene expression studies have also associated AKR1B10 with eating-disorders and nicotine dependence (M. W. Kang et al, 2011; Rohde et al, 2015). This is consonant with the gene’s decreased expression in the reward circuitry of rat strains that are more sensitive to the reinforcing properties of cocaine, morphine, and ethanol (Higuera-Matas et al, 2011).…”

Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of Keratinocyte

“…Currently, AKR1B10 is rarely reported to be related to psoriasis and is only shown to play an important role in liver carcinogenesis and eating behavior [ 33 ]. We observed that this gene was the highest DEG expressed in the psoriasis tissue compared to normal tissue.…”

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“…The deficiency in AKR1D1 is presented by neonatal cholestasis and liver failure in early infancy ( Zhao et al, 2023 ). Genetic variants in the AKR1B10 locus influence human eating behavior ( Rohde et al, 2015 ), AKR1C2 gene variants are linked to adipose tissue distribution ( Ostinelli et al, 2021 ), and certain gene variants of AKR1C3 contribute to interindividual susceptibilities to atopic dermatitis ( Vogeley et al, 2023 ). AKRs are also implicated in resistance to cancer chemotherapeutic agents, either because they are directly involved in their metabolism or because they help eradicate the cellular stress created by these agents ( e.g.…”