The Clinical Study Of KCNJ5 Gene Mutation In Adrenal Tissues With Patients Of Aldosterone-producing Adenomas And Unilateral Adrenal Hyperplasia

Objectives Primary Aldosteronism is one of the most common cause of leading to secondary hypertension.The main reason is inappropriately high Aldosterone production, relatively autonomous from the rennin-angiotensin system, and nonsuppressible by sodium loading and blood expansion. Aldosterone-producing adenomas and Unilateral adrenal hyperplasia are two subtype of Primary Aldosteronism. Because the both have the similar clinical phenotype and the surgical results. There are a few studies about weather or not the same pathogenessis of them. The KCNJ5 gene somatic mutation in patients with sporadic Aldosterone producing adenomas haved widely attented.we want to understanding the mutation and effect of KCNJ5 mutation in patients with Aldosterone-producing adenomas and Unilateral adrenal hyperplasia. Methods 1) Getting information of KCNJ5 gene in patients with APAs and UAH: Sequencing KCNJ5 gene from DNA and c DNA in Adrenal tissues and DNA in bloods of 46 Patients with Aldosterone-producing adenomas and Patients with Unilateral adrenal hyperplasia coming from The Peoples Hospital of Xin jiang Uyghur autonomous region from 2008 to 2011. 2) Meanwhile the basic clinical data(age, ethnic group, gender, BMI, plasma aldosterone, renin, serum potassium, urine potassium concentration, serum lipid, ultrasound indexes of heart and polysomnographic) were collected; â‘  To analyze the effect of KCNJ5 mutation to the clinical phenotypeof patients with APA and UAH; â‘¡ To compare the effect of KCNJ5 mutation to the clinical phenotype between APAs and UAH. Results: 1) The results of sequencing KCNJ5 gene in patients with APAs and UAH: â‘  Of the 46 patients with APAs and 14 patients had the same four types, somatic mutations of the KCNJ5 gene: p. G151 R and/or p. L168 R mutation. P.S209 T and P.L102 T and no mutation in blood. P.S209 T and P.L102 T were new mutation unreported. â‘¡ Of the 4 patients with APA, 9(19.57%) patients had two types, somatic mutations of the KCNJ5 gene: p. G151 R and/or p. L168 R mutation. 5 tumors are p. G151 R, 4tumors are p. L168 R, 9(26.07%) are P.S209 T and 14(30.43%) are P.S102 Q. 2) Clinical characteristic of KCNJ5 gene mutation in patients with APA and 14 patients: â‘  To compare average systolic pressure and serum potassium between the KCNJ5 mutation and wild type with APAs the differences had significance(P vlue was 0.042 and 0.048 respectively), The differences of average age, course, average systolic pressure, average diastolic pressure, sitting ALD, sitting renin activity, ARR, body mass index, high density lipoprotein, ejection fraction, left ventricular mass index and tumor diameter had no significance(P>0.05). The differences of average systolic pressure and average diastolic pressure had significance(P value was 0.032 and 0.016 respectively) in between the KCNJ5 mutation and wild type with UAH. â‘¡ To compare the Clinical characteristic of KCNJ5 gene among G151 R, L168 R, S209 T, L102 Q and wild type mutation in patients with APAs. The differences of average systolic pressure, average diastolic pressure, serum potassium, high density lipoprotein and left ventricular mass index had significance(P value was 0.005, 0.003, 0.003, 0.023 and 0.004 respectively) between G151 R and wild type. The difference of tumor diameter had significance(P=0.027) between L168 R and wild type. The differences of average diastolic pressure, sitting ALD, serum potassium, high density lipoprotein and EF had significance(P value was 0.045, 0.025, 0.030, 0.024 and 0.002 respectively) between L102 Q and wild type.There was no significance between S209 T and wild type. â‘¢ To compare the Clinical characteristic of KCNJ5 gene among G151 R, L168 R, S209 T and L102 Q between APAs and UAH. The differences of average systolic pressure, average diastolic and serum potassium had significance(P value was 0.007, 0.009 and 0.033respectively) between APAs and UAH of G151R+L168R. The differences of BMI and cholesterol had significance(P value was 0.025 and 0.005) between APAs and UAH of S209 T. The differences of average diastolic pressure, sitting ALD, cholesterol and EF had significance(P value was 0.022, 0.027 and 0.033respectively) between APAs and UAH of L102 Q, â‘£4 case(3male/1female) with sever obstructive sleep apnea-hypopnea syndrome in 14 patients with unilateral adrenal hyperplasia. Conclusion: 1) Mutation of KCNJ5 gene G151R(heterozygous), L168 R, S209 T and L102 Q were in patients with APAs,.The patients with UAH had the same mutation, Mutation rate was 65.21%(30/46) and 71.43%(10/14) respectively, P.S209 T and P.L102 T were new mutation unreported. It is different from past study showed the distribution of these mutations among human populations is apparently different from one ethnicgroup to another. 2) The clinical symptoms of patients with KCNJ5 mutation in APAs were more serious than no mutation, the order severity was G151 R, L102 Q, L168 R and S209 T. 3) The effect of KCNJ5 mutation was more serious in patients with APAs than UAH, the order severity was G151 R, L102 Q, L168 R and S209 T.4.The patienst with APAs and UHA had the same mutation of KCNJ5, however, The effect of KCNJ5 mutation was different, the pathogenesis is not and still need futher research. 6) It is still need to be further studied the mutation of KCNJ5 gene is or not related with OSAHS.