Abstract：
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.
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.
摘要：
目的：脂肪水肿是一种主要影响女性的慢性疾病，特征是脂肪在对称的异常积累，四肢的双侧模式，经常与荷尔蒙失衡相吻合。
方法：尽管据推测性激素在其病因学中的作用，确定的联系仍然难以捉摸。本研究探讨了在Aldo-keto还原酶成员C2（AKR1C2）的C末端区域内存在突变缺失的患者的情况。Ser320PheTer2，这可能导致酶活性升高。本研究纳入了另外19名脂肪瘤患者和另外2名受影响的家庭成员14的队列。另外两名受影响的家庭成员是患有AKR1C1L213Q变体的患者的亲属，这包括在19个队列中，并在文献中进行了描述。
结果：我们的调查显示AKR1C2过度表达，通过qPCR定量，在21例（24％）无AKR1C2基因突变的脂水肿患者中，有5例。总的来说，这些发现暗示AKR1C2在脂水肿的发病机制中，证实其因果关系。
结论：这项研究表明，该酶的激活突变或其过度表达是脂水肿发展的致病因素。在不同人群中的进一步探索和复制将增强我们对这一重要联系的理解。
方法：尽管据推测性激素在其病因学中的作用，确定的联系仍然难以捉摸。本研究探讨了在Aldo-keto还原酶成员C2（AKR1C2）的C末端区域内存在突变缺失的患者的情况。Ser320PheTer2，这可能导致酶活性升高。本研究纳入了另外19名脂肪瘤患者和另外2名受影响的家庭成员14的队列。另外两名受影响的家庭成员是患有AKR1C1L213Q变体的患者的亲属，这包括在19个队列中，并在文献中进行了描述。
结果：我们的调查显示AKR1C2过度表达，通过qPCR定量，在21例（24％）无AKR1C2基因突变的脂水肿患者中，有5例。总的来说，这些发现暗示AKR1C2在脂水肿的发病机制中，证实其因果关系。
结论：这项研究表明，该酶的激活突变或其过度表达是脂水肿发展的致病因素。在不同人群中的进一步探索和复制将增强我们对这一重要联系的理解。
