KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness

被引:9
|
作者
Chang, Yi-Yao [1 ,2 ,3 ,4 ,5 ]
Pan, Chien-Ting [6 ]
Chen, Zheng-Wei [6 ]
Tsai, Cheng-Hsuan [3 ,4 ,7 ]
Peng, Shih-Yuan [3 ,4 ]
Chang, Chin-Chen [4 ,8 ]
Lee, Bo-Ching [4 ,8 ]
Liao, Che-Wei [9 ]
Peng, Kang-Yung [3 ,4 ]
Chiu, Yu-Wei [2 ,10 ]
Chou, Chia-Hung [4 ,11 ]
Wu, Vin-Cent [4 ,12 ]
Liu, Li-Yu Daisy [13 ]
Hung, Chi-Sheng [3 ,4 ,14 ]
Lin, Yen-Hung [3 ,4 ,14 ]
机构
[1] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 100, Taiwan
[2] Far Eastern Mem Hosp, Cardiol Div, Cardiovasc Med Ctr, New Taipei 220, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Internal Med, Div Cardiol, Taipei 100, Taiwan
[4] Natl Taiwan Univ, Coll Med, Taipei 100, Taiwan
[5] Chihlee Univ Technol, Ctr Gen Educ, New Taipei 220, Taiwan
[6] Natl Taiwan Univ Hosp, Dept Internal Med, Yun Lin Branch, Yunlin 640, Taiwan
[7] Natl Taiwan Univ Hosp, Dept Internal Med, Jin Shan Branch, New Taipei 220, Taiwan
[8] Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei 100, Taiwan
[9] Natl Taiwan Univ Canc Ctr, Dept Med, Taipei 106, Taiwan
[10] Yuan Ze Univ, Dept Comp Sci & Engn, Taoyuan 320, Taiwan
[11] Natl Taiwan Univ Hosp, Dept Obstet & Gynecol, Taipei 100, Taiwan
[12] Natl Taiwan Univ Hosp, Dept Internal Med, Div Nephrol, Taipei 100, Taiwan
[13] Natl Taiwan Univ, Dept Agron, Biometry Div, Taipei 106, Taiwan
[14] Natl Taiwan Univ Hosp, Cardiovasc Ctr, Taipei 100, Taiwan
关键词
KCNJ5 somatic mutation; pulse wave velocity; aldosterone-producing adenoma; adrenalectomy; propensity score matching; arterial stiffness; PULSE-WAVE VELOCITY; LEFT-VENTRICULAR HYPERTROPHY; K+ CHANNEL MUTATIONS; DIAGNOSTIC-ACCURACY; META-REGRESSION; BLOOD-PRESSURE; ADRENALECTOMY; METAANALYSIS; HETEROGENEITY; PREVALENCE;
D O I
10.3390/cancers13174313
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Primary aldosteronism (PA) is the most common form of secondary hypertension and induces various cardiovascular injuries. Aldosterone-producing adenoma (APA) is one of the major forms of PA. The occurrence of APA is closely correlated with somatic mutations, including KCNJ5. We described here the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of age, sex, and blood pressure status. We found KCNJ5 mutation carriers had similar arterial stiffness before surgery, but greater improvement of arterial stiffness after adrenalectomy compared with non-carriers. Hence, APA patients with KCNJ5 mutations had a greater improvement in arterial stiffness after adrenalectomy than those without mutations. Primary aldosteronism is the most common form of secondary hypertension and induces various cardiovascular injuries. In aldosterone-producing adenoma (APA), the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of confounding factors is uncertain. We enrolled 213 APA patients who were scheduled to undergo adrenalectomy. KCNJ5 gene sequencing of APA was performed. After propensity score matching (PSM) for age, sex, body mass index, blood pressure, number of hypertensive medications, and hypertension duration, there were 66 patients in each group with and without KCNJ5 mutations. The mutation carriers had a higher aldosterone level and lower log transformed brachial-ankle pulse wave velocity (baPWV) than the non-carriers before PSM, but no difference in log baPWV after PSM. One year after adrenalectomy, the mutation carriers had greater decreases in log plasma aldosterone concentration, log aldosterone-renin activity ratio, and log baPWV than the non-carriers after PSM. Only the mutation carriers had a significant decrease in log baPWV after surgery both before and after PSM. KCNJ5 mutations were not correlated with baseline baPWV after PSM but were significantly correlated with increment baPWV after surgery both before and after PSM. Conclusively, APA patients with KCNJ5 mutations had a greater regression in arterial stiffness after adrenalectomy than those without mutations.
引用
收藏
页数:13
相关论文
共 50 条
  • [21] KCNJ5 mutations in aldosterone producing adenoma and relationship with adrenal cortex remodeling
    Boulkroun, Sheerazed
    Dzib, Jose-Felipe Golib
    Samson-Couterie, Benoit
    Rosa, Fabio Luiz Fernandes
    Rickard, Amanda Jane
    Meatchi, Tchao
    Amar, Laurence
    Benecke, Arndt
    Zennaro, Maria-Christina
    MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2013, 371 (1-2) : 221 - 227
  • [22] A NOVEL INSERTIONAL SOMATIC KCNJ5 MUTATION IN AN AUSTRALIAN PATIENT WITH AN ALDOSTERONE PRODUCING ADENOMA
    Xu, S.
    Hardege, I.
    Murthy, M.
    Gordon, R.
    Stowasser, M.
    O'Shaughnessy, K.
    JOURNAL OF HYPERTENSION, 2015, 33 : E120 - E120
  • [23] Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas
    Murakami, Masanori
    Yoshimoto, Takanobu
    Nakabayashi, Kazuhiko
    Nakano, Yujiro
    Fukaishi, Takahiro
    Tsuchiya, Kyoichiro
    Minami, Isao
    Bouchi, Ryotaro
    Okamura, Kohji
    Fujii, Yasuhisa
    Hashimoto, Koshi
    Hata, Ken-Ichiro
    Kihara, Kazunori
    Ogawa, Yoshihiro
    ENDOCRINE-RELATED CANCER, 2017, 24 (10) : 531 - 541
  • [24] Effect of KCNJ5 Mutations on Gene Expression in Aldosterone-Producing Adenomas and Adrenocortical Cells
    Monticone, Silvia
    Hattangady, Namita G.
    Nishimoto, Koshiro
    Mantero, Franco
    Rubin, Beatrice
    Cicala, Maria Verena
    Pezzani, Raffaele
    Auchus, Richard J.
    Ghayee, Hans K.
    Shibata, Hirotaka
    Kurihara, Isao
    Williams, Tracy A.
    Giri, Judith G.
    Bollag, Roni J.
    Edwards, Michael A.
    Isales, Carlos M.
    Rainey, William E.
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (08): : E1567 - E1572
  • [25] Genetics of aldosterone-producing adenomas with pathogenic KCNJ5 variants
    Lerario, Antonio M.
    Nanba, Kazutaka
    Blinder, Amy R.
    Suematsu, Sachiko
    Omura, Masao
    Nishikawa, Tetsuo
    Giordano, Thomas J.
    Rainey, William E.
    Else, Tobias
    ENDOCRINE-RELATED CANCER, 2019, 26 (04) : 463 - 470
  • [26] Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma
    Scholl, Ute I.
    Abriola, Laura
    Zhang, Chengbiao
    Reimer, Esther N.
    Plummer, Mark
    Kazmierczak, Barbara I.
    Zhang, Junhui
    Hoyer, Denton
    Merkel, Jane S.
    Wang, Wenhui
    Lifton, Richard P.
    JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (07): : 2739 - 2750
  • [27] KCNJ5 mutation as a predictor for resolution of hypertension after surgical treatment of aldosterone-producing adenoma
    Kitamoto, Takumi
    Omura, Masao
    Suematsu, Sachiko
    Saito, Jun
    Nishikawa, Tetsuo
    JOURNAL OF HYPERTENSION, 2018, 36 (03) : 619 - 627
  • [28] Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma
    Kitamoto, Takumi
    Nishikawa, Tetsuo
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (16)
  • [29] Mutations of the Potassium Channel KCNJ5 Causing Aldosterone-Producing Adenomas One or Two Hits?
    Gomez-Sanchez, Celso E.
    Gomez-Sanchez, Elise P.
    HYPERTENSION, 2012, 59 (02) : 196 - 197
  • [30] Primary aldosteronism diagnostics: KCNJ5 mutations and hybrid steroid synthesis in aldosterone-producing adenomas
    Rege, Juilee
    Turcu, Adina F.
    Rainey, William E.
    GLAND SURGERY, 2020, 9 (01) : 3 - 13