【摘要】 目的观察血清脂联素(APN)水平及APN基因启动子区域单核苷酸多态性(SNP)频率与高血压(HP)及其合并症间的相关性,探讨脂联素基因(aPM1)多态性与HP及合并症间的遗传危险因素。并确立一种高效、准确、经济的检测APN基因实用筛查方法,供临床检测应用。方法对单纯HP组(1组)、HP合并T2DM(HP-T2DM)组(2组)、HP合并冠心病(H-CHD)组(3组)、HP合并肾病(HP-NE)组(4组)和对照组(5组)分别测定空腹血清APN及生化指标。采用变性高效液相色谱(DHPLC)技术,筛选APN基因多态性位点。结果在APN基因(aPM1)启动子区-11377位点存在单核苷酸多态性(GG、GC、CC)。GG、GC、CC基因频率在HP组和对照组间有显著性差异(P<0.05),aPM1的SNP-11377位点G等位基因频率在HP组明显高于对照组(χ2=6.71,OR=0.65,P=0.031)。血清APN水平与HDL呈正相关(r=0.497,P=0.006).通过对实验条件优化,在采用DHPLC技术检测APN基因多态性位点时发现,本实验检测柱温以60℃最佳。结论血清APN水平与血清HDL之间呈正相关,表明APN也可能是心血管的保护因子。aPM1启动子区SNP-11377C/G多态性与HP及并发症的发生和HP患者体型肥胖形成机制有相关性,提示SNP-11377C/G多态性可能增加HP的遗传风险。更多还原

【Abstract】 Objective To explore the correlation of adiponectin(APN)genetic single nucleotide polymorphism(SNP) frequency in patients with hypertension(HP) and its complications. It is expected,by comparing the SNP frequency of some regions in APN gene promoter of HP and non-HP,to discover the related genes affecting the development ofHP;to explore whether the mutation of(APN)gene is a risk factor in inheritance of HP,and to set up a highly efficient,accurate,economical and practical screening method to detect the mutation of APN in clinical practice.Methods According to the diagnostic criteria of HP,coronary heart disease(CHD),type 2 diabetes(T2DM),and diabetic nephropathy(NE),In simple HPgroup,HP-T2DM,HP-CHD,HP-NE and the control group.Serum biochemistry item are measured.The technique of denaturing high-performance liquid chromatography(DHPLC) is used to detect SNP of ANP gene.Results As the fragment amplified in the region of promoter of APN gene is compared with APN GeneID: 9370 sequence landed in GenBank,point mutation has been developed(-11377G/C).This sequence has been landed in GenBank,the Landing No: EF 581829,which is at present the first domestic landing of-11377G/C site of APN gene in GenBank.This study demonstrates: The frequency of G allele with Landing No: EF 581829 is related with incidence of HP,and is a risk factor of HP.The relative risk of GC to CC in developingHP:OR=0.65.By comparing the clinical data of different groups of genotype in HP,it may be seen that the genotype affects systolic blood pressure,BMI,abdominal circumference,and waist-buttock ratio(P=0.02)After optimizing the experimental conditions,it is found Where using DHPLC technology to estimate SNP of APN gene,the column temperature has a profound influence on the peak shape of DHPLC.In this experiment,to measure at the column temperature 60℃ is optimal.Conclusion Serum HDL is the main factor affecting serum APN,and the two are in positive correlation.This result suggests that: fall of serum APN level will decrease its cardiovascular protective action in HP patients,indicating APN is possibly also a cardiovascular protective factor.SNP-11377G/C site of APN gene G allele has a definite correlation with complications of hypertension in HP patients,and and may contribute to the genetic risk for HP.更多还原