Study On Correlation Between Variants In Pathogenic Genes Of Monogenic Hypertension And Hypertension In Young Adults

Objective We aimed to investigate the effect of rare variants in pathogenic genes of monogenic hypertension on blood pressure,RAAS hormone levels and biochemical indicators of young hypertensive patients,and explore the prevalence of monogenic hypertension in young hypertensive patients.Methods Inclusion criteria:patients who suffered from hypertension from the age of 14 to 40 years old,no matter of male or female.Exclusion criteria:firstly,participants who were diagnosed with secondary hypertension as follows:renal artery stenosis,renomocytoma,Cushing's syndrome,primary aldosteronism,hyperthyroidism,coarctation of the aorta,and hyperthyroidism included;secondly,patients who were taking anti-hypertensive drugs(angiotensin-converting enzyme inhibitors,angiotensin receptor blockers,beta-receptor antagonists,diuretics,)that may influence the measurement of RAAS hormone levels or stopped the medicine less than four weeks.Clinical data of age,sex,age of onset,family history of hypertension,weight,height,history of smoking,heart rate,blood pressure were collected.And laboratory data of electrolytes,blood lipids,uric acid,and creatinine were collected.Genetic sequencing was performed on all participants,and calculated the number of rare variants in pathogenic genes of monogenic hypertension.The number of rare variants,age,history of smoking,body mass index,family history of hypertension,hyperuricemia,serum potassium,serum sodium,total cholesterol,triglyceride was defined as independent variables,and blood pressure as dependent variable.The relationship between these independenthe hypertensive patients were analyzed by the principal component regression t variables and blood pressure of analysis.In addition,we analysed the the effect of rare variants in pathogenic genes of monogenic forms of low-renin hypertension on RAAS hormone levels and biochemical indicators of young hypertensive patients.Results A total of 44 patients who were hospitalized in Guangdong General Hospital from November 2016 to October 2017 were enrolled,among whom 24 patients were male and 20 patients were female.The average age of onset was 30.1±7.6 years.95 rare variants were detected in all participants.Systolic blood pressure in young hypertensive patients was positively correlated with age and the number of rare mutations.Based on the presence or absence of rare variants in pathogenic genes of monogenic low-renin hypertension,all participants were divided into rare variants carriers(group A)and non-rare variants carriers(group B).Then according to different pathogenic genes,group A were divided into three subgroups of A1,A2 and A3.Patients only carried rare variants in pathogenic genes of GS were marked group A1;patients only carried rare variants that were not in pathogenic genes of GS were marked group A2;the remaining rare variants carried patients were marked group A3.There were 17 patients in group A,and 26 patients in group B.PRA and Ang I levels were significantly lower in group A compared with group B(P<0.01).The average serum potassium concentrations in the groups of A1,A2,A3 and B were ranked as follows:A1>B>A3>A2,the serum potassium concentrations were not statistically significant in the four groups(F=1.85,P=0.15).Moreover,a patient suspected to diagnose with FH-IV,carried a variant of CACNA1HR1482Q(rs372132309)were found in this study.ConclusionsFirstly,the number of rare variants in pathogenic genes of monogenic hypertension was related with systolic blood pressure in young hypertensive patients.Secondly,rare variants in pathogenic genes of monogenic forms of low-renin hypertension was associated with the decrese of PRA and Ang I levels in young hypertensive patients.Thirdly,we found a patient suspected to diagnose with FH-IV,maybe we found a new pathogenic variants of FH-IV.