The Association Of β-AR Genotype With Phenotype And Their Guiding Significance To EH Individual Therapy

Background and objectiveThere are three β-adrenoceptor(β-AR) subtypes had been cloned up to now. Every subtype has a lot of gene polymorphism situs, which play important roles in cardiovascular system physiological function and the occurrence and development of diseases. Heart period signal (HPS) analysis is used as a non-invasive heart autonomic nervous system (ANS) function examination, which has been acknowledged and used extensively in clinic. This research is designed to analyze the associations between the five single nucleotide polymorphisms(SNPs) of threeβ-AR subtypes and heart rate(HR),blood pressure(BP), HPS and pulse pressure(PP) ,and to investigate the association of essential hypertension(EH) susceptibility with β-AR SNPs, then to guide EH individual therapy withβ-AR SNPs, ACE I/D and HPS spectral parameters. Methods1.The detection of SNPs: PCR-RFLP technique was used to determine Ser49Gly and Arg389Gly polymorphism of the β1-AR gene, Trp64Arg polymorphism ofβ3-AR gene. Allele specific-PCR technique was used to determine Arg16Gly and Gln27Glu polymorphism ofβ2-AR gene. ACE I/D polymorphism was determined by PCR.2.The detection of HR: HR was detected by computerized system for analyzing electrocardiosignal for 8 minutes.3.The detection of HPS: HPS of four body postures (supine, left lateral, right lateral and standing) were detected by computerized system for analyzing electrocardiosignal for 8 minutes. HPS spectral parameters were analyzed by FFT. 4.The detection of BP: the BP of right upper arm was got by auscultation with standard mercury column sphygmomanometer. The descending speed of the mercury column was 2 mmHg/s. When the first Korotkoff sound was heard, the corresponding pressure was considered as systolic pressure (SBP). When the fifth Korotkoff sound was heard, the corresponding pressure was considered as diastolic pressure (DBP). The BP were measured three times interval two minutes and the mean was considered as BP value.5.The detection of therapy effect: EH subjects were administered imidapril therapy, 5mg/d, 8～10Am,po, ×4 weeks.β-AR and ACE I/D polymorphism were detected. HPS spectral parameters and BP were detected for 7 times (before therapy, 1 day, 4 days, 1week, 2 weeks, 3 weeks, 4 weeks after therapy).Results1.The association ofβ-AR SNPs with RHR: The Arg389Gly polymorphism ofβ1-AR gene was significantly associated with RHR (P<0.05). The individuals with Gly/Gly had the highest RHR (female: 80.54±3.70, male: 85.73±0.72), with Arg/Arg had the lowest RHR (female: 70.65±8.60, male: 69.04±8.56), and with Arg/Gly had RHR intermediate to those of either type of homozygote (female: 72.21±8.33, male: 78.89±7.05). No significant association was found between Ser49Gly, Arg16Gly, Gln27Glu and Trp64Arg polymorphism with RHR respectively.2.The association ofβ-AR SNPs with HPS spectral parameters: The Arg389Gly polymorphism ofβ1-AR gene and Trp64Arg polymorphism ofβ3-AR gene were significantly associated with HPS (P<0.05).No significant association was found between Ser49Gly, Arg16Gly and Gln27Glu polymorphism with HPS respectively. When body posture changed in "supine→left lateral→right lateral→standing" sequence, the change trends of APU and TPV ofβ1-AR Arg389Gly were Arg/Arg progressively increased ,Arg/Gly had no regularity ,Gly/Gly progressively decreased；The change trend of APH was Arg/Arg progressively decreased, Arg/Gly had no regularity ,Gly/Gly progressively increased. The change trends of APU and TPV of β3-AR Trp64Arg were Trp/Trp progressively decreased, Trp/Arg had no regularity,Arg/Arg progressively increased；The change trend of APH was Trp/Trp progressively increasd, Trp/Arg had no regularity,Arg/Arg progressively decreased. In supine, HPS sprectrum parameter change ofβ1-AR Arg389Gly were APUGly/Gly>APUArg/Gly>APUArg/Arg(591.80±42.33 >565.91±46.22 >524.35±48.70)and APHArg/Arg> APH Arg/Gly> APH Gly/Gly(415.07±55.17 >364.51±47.05 >338.20±35.60).3.The as...