title: Prevalence and characterization of somatic mutations in Chinese aldosterone-producing adenoma patients.
abstract: Recently somatic mutations of KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been identified in patients with aldosterone-producing adenoma (APA). The present study sequenced the DNA in the tissues and blood samples from Chinese patients with APA for KCNJ5, ATP1A1, ATP2B3, and CACNA1D gene mutations.Among the 114 patients, 86 (75.4%) were identified with KCNJ5 somatic mutations, including 3 previously reported (G151R, L168R, T158A) and 2 other unreported mutations. One patient presented with both a point mutation (E147) and an insertion mutation, whereas another had a 36-base duplication, G153_G164dup. No mutation of ATP1A1 and ATP2B3 in the known hotspots was identified and only 1 male patient was detected with a novel CACNA1D mutation, V748I. Unlike other studies, male and female patients had similar KCNJ5 mutation rates (76.9% vs 74.2%). Mutation carriers were younger and had lower preoperative potassium level, whereas male (but not female) mutation carriers had higher preoperative plasma aldosterone concentration and preoperative blood pressures. Mutation carriers also had higher LV mass index (LVMI) than nonmutation carriers. After surgery, LVMI improved significantly in the KCNJ5 mutation group but not in the nonmutation group. The mRNA expression of KCNJ5, CYP11B2, and ATP2B3 was higher in the KCNJ5-mutated APA tissues. Functional characterization of the 2 novel KCNJ5 mutations showed that they were associated with decreased proliferation, membrane depolarization, elevated secretion of aldosterone, and increased expression of CYP11B1 and CYP11B2.In conclusion, Chinese APA patients appear to have a high frequency of somatic KCNJ5 mutation. Mutation prevalence rates are similar among men and women and 2 novel mutations are identified. KCNJ5-mutated patients benefit more from surgical resection of APA than nonmutated patients.
authors.affiliation: From the State Key Laboratory of Kidney Disease, Department of Urology (BW, XL, XZ, XM, LC, YZ, XL, YT, QH, YG, YF); Department of Outpatient Officer Consultation Room, PLA Medical School, Chinese People's Liberation Army General Hospital, Beijing, China (JO).
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
authors.forename: Xintao
authors.initials: X
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Luyao
authors.initials: L
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Lyu
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Tang
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000378:metabolism*; D044466:Asian People; D020746:Calcium Channels, L-Type / Q000235:genetics; D018929:Cell Culture Techniques; D002681:China / Q000453:epidemiology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D020869:Gene Expression Profiling; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012333:RNA, Messenger / Q000096:biosynthesis; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D012333:RNA, Messenger; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase