| BackgroundEssential hypertension (EH) is regarded as a multifactor and polygenetic disorder now. one third of the variance of blood pressure is caused by hereditary factor. With the rapid development of molecular biology technique, the mechanisms and candidate genes of essential hypertension have been put more and more attention . Recent researches have shown that heterotrimeric guanine nucleotide binding regulatory protein (G-protein) plays an important role in the trans-membrane signaling process and is involved in vascular events. G-proteins intracellular signal transduction regulates Vasomotion, synthsis ,Secretion, differentiation , concrescence of vascular smooth muscle cell and so on . So it is vital to maintain the integrality of vascular wall and adjust vascular tension. Doubtlessly. quantitative change and functional disorder of G protein is significantly associated with hypertension. Since siffert et al demonstrated that the correlation between polymorphism of G protein β3 subunit and essentialhypertension in 1998, more and more researches have been focused on it . But no uniform conclusions can be drawn.Moreover, in the process of studying the pathogenesis of essential hypertension , insulin resistance (IR)has been considered an independent risk factor. IR can not only accelerate the deterioration of hypertension but also result in target organ damage. We know IR has complicated expressivity , it has a obviously hereditary tendency. Studise in human metabolism of glucose by molecular biology technique have shown that in the course of the insulin secretion and transport of cystoid bubbles , the adjustment of G-protein is necessary in each link, especially GfSysubunit. However , weather there is a strict relationship between G-proteins mediate intracellular signal transduction and essential hypertension and insulin resistance complications has not been clear. ObjectivesThe experiment was designed to investigate the correlation between G protein P3 subunit (GNB3) C825T polymorphism and blood pressure and hypertension with insulin resistance through measuring fasting blood glucose , 2h postprandial glucose ,fasting insulin, C-peptide and Insulin resistance index in EH patients and control subjects . Furthermore , to explore the pathogenesis of essential hypertension with insulin resistance in the level molecular biology and give help to clinical diagnosis and prevention of complication. Methods110 essential hypertension patients (outpatients from April to July in 2004) and 50 matched controls were selected .There was no statistic difference between two groups in age,sex and body weight.All samples were extracted DNA by whole blood genomic DNA purification kit. Genotypes of the polymorphisms were determined by polymerase chain reaction (PCR) and PCR products were digested by restriction endonucleases . glucose was measured by glucose oxidase test ,the measurement of insulin and C-peptide were used radio-immune assay, relative insulin resistance expressed by the homeostatic model assessment HOMA —IR[fasting insulin (mU L"1) x fasting glucose (mmol L"')/22.5]o Results1.Compared with control, frequency of the genetype and allele was not statistically significant differences in essential hypertension(P>0.05). CT genetype appears to be more common in two groups .TT genetype close significant difference(P=0.052). But get not to statistical significance .2. The GNB.i825TT genotype was associated with a significantly systolic BP higher risk than CC and CT in essential hypertension patients (p<0.001). Diastolic BP levels was no differet among them .No statistical differences of systolic BP and Diastolic BP can be observed between CC and CT genetype.3. The indexes of clinical biochemics relevanting to metabolism glucose shown that there were higher fasting blood glucose ,higher 2h postprandial glucose and higher fasting serum insulin levels in essential hypertension than in control group. In essential hypertension group, Blood glucose,2h postprandial glucose and serum insulin levels were significant difference between T-allele carriers and non-carriers(each P=0.002>P=0.001 ^P=::0.034),but there was no difference between CC and CT. No significant difference can be observed about C-peptide between each genetype .4. Relative insulin resistance was found to be significantly higher in carriers of the T allele in the group of hypertension(P<0.05) , especially in male subjects with abdominal body fat distribution (waist-to-hip ratio >0.85)(P<0.001). No effect was observed in women or men with a waist-to-hip ratio <0.85. Multiple regression analysis revealed that the IR content is independently associated with BMI. Conclusions1. The results demonstrate that the GNB, TT genetype is associated with systolic BP levels of essential hypertension , TT genetype may be a risk factor of essential hypertension.2.There was metabolic dysfunction of glucose in hypertension patients: higher fasting blood glucose ,higher 2h postprandial glucose and higher fastingserum insulin levels.3. The results suggest a relationship between the 825T allele of GNB3 and insulin resistance in the essential hypertensive patients studied, which seems to be independent of BMI. especially in men with abdominal fat distribution .This evidence suggests a possible further association of the C825T dimorphism with insulin resistance,or serves as an early genetic marker of impaired glucose tolerance of hypertension.
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