The Sequencing Of KCNJ5Gene In Aldosterone-producing Adenoma In Xinjiang Region

Objective This study is about to detect the KCNJ5gene variations in aldosterone-producingadenoma(APA) of the Primary aldosteronism（PA），and to investigate the association betweenPA and KCNJ5gene variations.Methods46APA tumors and their Clinical characteristics were collected fromHypertension Center of the People’s Hospital of Xinjiang Uygur Autonomous Region, and allthe tumors were confirmed by pathology. Peripheral blood samples of the same patients werealso collected as control. All the samples of the coding region segments of KCNJ5weredetected by PCR and direct DNA sequencing to compare the different missense mutations inthe tumor cells and peripheral blood cells and to analyze the association between the genotypeand phenotype. Protein structure and function were also predicted by specific software.Results Three missense mutations were found in46patients with APA: c.451G>C/A(p.G151R)(5/46),c.503T>G(p.L168R)(4/46), c.830T>A(p.S209T)(12/46). S209T, as theunreported somatic mutation was observed. There were no missense mutations detected in theperipheral blood.Protein structure prediction suggests that KCNJ5mutations may associatewith APA. Sex,Age,SBP,DBP,duration of hypertension, plasma potassium, urine potassium,ALD,PRA,ARR, diameter and the rate of positive family history were compared between themutants and wild-type, SBP and plasma potassium level among G151R,L168R and S209Thad statistical differences. The SBP level of G151R was significantly higher than the othertwo groups. Potassium was significantly lower than the other two groups. comparing with thewild-types, the mutants of G151R had higher SBP,DBP levels,and plasma potassium levelswere lower. The mutants of L168R had tumor diameter than the wild-type.12Somatic SNPswere found in46patients with APA.-20120G/C (1/46) in the promoter region and5521T/A(27/46) in intron region were observed as the new SNPs.Conclusions Three missense mutations and12Somatic SNPs were found in46patientswith APA.S209T,-20120G/C and5521T/A were observed as the new variations.The subjectswith mutations had more serious condition than subjects without mutations after comparingtheir clinical phenotype. G151R and L168R maybe more important for the pathogenesis of PA.And other different subtypes may exist in PA.