Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany.
Deggendorf Institute of Technology, Deggendorf, Germany.
Exp Clin Endocrinol Diabetes. 2024 Nov;132(11):608-613. doi: 10.1055/a-2408-0718. Epub 2024 Sep 18.
Endogenous hypercortisolism presents with variable phenotypes. Etiological factors accounting for the level of hypercortisolism or varying severity of associated comorbidities are lacking. Recently, the adrenal ATP-binding cassette B1 (ABCB1) gene was identified as a modulator of glucocorticoid secretion.
To evaluate the effect of ABCB1 polymorphism rs2032582 on steroid metabolome and clinical phenotypes in patients with endogenous hypercortisolism.
In this cross-sectional cohort study, 137 patients prospectively enrolled in the German Cushing's registry were included (41 with ACTH-producing pituitary adenoma, 21 with cortisol-producing adrenal adenoma, and 75 with excluded hypercortisolism). In all patients, ABCB1 polymorphism was analyzed using a TaqMan genotyping assay, glucocorticoid metabolite excretion in 24-hour urine samples was analyzed by gas chromatography-mass spectrometry, and the clinical phenotype was assessed systematically.
In patients with cortisol-producing adrenal adenomas, but not in patients with ACTH-producing pituitary adenomas, homozygous major allele GG of ABCB1 polymorphism rs2032582 was associated with higher overall cortisol metabolite secretion (median 13515 [IQR 10347; 25669] µg/24h vs. 9645 [6146; 10732] µg/24h in minor homo- and heterozygotes, p=0.036) and elevated major cortisol metabolites αTHF, THF and THE (9339 [6929; 17789] µg/24h vs. 6288 [4184; 7455] µg/24h, p=0.045). Moreover, these patients showed higher mean arterial pressure (116 [111; 131] mmHg in major homozygotes vs. 105 [96; 112] mmHg in minor homo- and heterozygotes, p=0.036).
The genotype of drug transporter gene ABCB1 rs2032582 polymorphism is associated with the degree of cortisol metabolite secretion in cortisol-producing adrenal adenomas and could, therefore, represent a modifier of disease severity in this context.
内源性皮质醇增多症表现出不同的表型。导致皮质醇增多症水平或相关合并症严重程度不同的病因因素尚不清楚。最近，肾上腺三磷酸结合盒 B1（ABCB1）基因被鉴定为糖皮质激素分泌的调节剂。
评估 ABCB1 多态性 rs2032582 对内源性皮质醇增多症患者类固醇代谢组学和临床表型的影响。
在这项横断面队列研究中，前瞻性纳入了德国库欣氏登记处的 137 名患者（41 名 ACTH 产生垂体腺瘤患者、21 名皮质醇产生肾上腺腺瘤患者和 75 名排除性皮质醇增多症患者）。在所有患者中，使用 TaqMan 基因分型检测分析 ABCB1 多态性，通过气相色谱-质谱法分析 24 小时尿液样本中的糖皮质激素代谢产物排泄情况，并系统评估临床表型。
在皮质醇产生的肾上腺腺瘤患者中，但在 ACTH 产生的垂体腺瘤患者中，ABCB1 多态性 rs2032582 的纯合子主要等位基因 GG 与更高的总皮质醇代谢产物分泌相关（中位数 13515 [IQR 10347; 25669] µg/24h 与次要同型和杂合子中的 9645 [6146; 10732] µg/24h，p=0.036）和升高的主要皮质醇代谢物 αTHF、THF 和 THE（9339 [6929; 17789] µg/24h 与 6288 [4184; 7455] µg/24h，p=0.045）。此外，这些患者的平均动脉压更高（主要纯合子为 116 [111; 131] mmHg，与次要同型和杂合子中的 105 [96; 112] mmHg 相比，p=0.036）。
药物转运蛋白基因 ABCB1 rs2032582 多态性的基因型与皮质醇产生的肾上腺腺瘤中皮质醇代谢产物的分泌程度相关，因此可能是该疾病严重程度的修饰因子。
