Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors

Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. Despite the conjectured role of sex hormones in its etiology, a definitive...

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Bibliographic Details
Published in:	European review for medical and pharmacological sciences Vol. 27; no. 6 Suppl; p. 127
Main Authors:	Kaftalli, J, Donato, K, Bonetti, G, Dhuli, K, Macchia, A, Maltese, P E, Louise Herbst, K, Michelini, S, Chiurazzi, P, Hill, M, Marceddu, G, Bernini, A, Bertelli, M
Format:	Journal Article
Language:	English
Published:	Italy 01-12-2023
Subjects:	Aldo-Keto Reductases - genetics Female Humans Hydroxysteroid Dehydrogenases - genetics Lipedema Mutation
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Summary:	Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature. Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role. This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.
ISSN:	2284-0729
DOI:	10.26355/eurrev_202312_34697