| Background: Essential hypertension is the most common cardiovascular diseases. It has been a high morbidity in China for 50 years, especially in older people. Peripheral arterial occlusive disease (PAOD) and heart, brain and vessel diseases had the same risk factor, PAOD is maker of vessel atherosclerosis (AS) in body. Male gender is an independent risk factor of heart disease, which has indicated the probability relationship between androgen (A) and heart disease. It was proved that there had been lower androgen in CHD, essential hypertension (EH) and obese.Androgens act through the androgen receptor (AR). The active of androgen receptor is controlled by androgen receptor gene. The relationship between androgen receptor gene (CAG)n polymorphism and the level of androgen is not clear. We analyzed androgen receptor in peripheral lymphocyte by flow cytometry, and set up the method. We were planning to clarify the relation between androgen and essential hypertension from aspects of androgen- androgen receptor- androgen receptor gene. It would give us a new way to prevent essential hypertension and atherosclerosis.Part OneStudy of Androgen and Androgen Receptor Associated with Hypertension and PAOD in Older MenObjective: To investigate the hormones and androgen receptor level associated with essential hypertension and PAOD in older men.Methods: A case control study was performed in 172 hypertensive patients, 44 peripheral arterial occlusive patients and 104 controls, which were randomly selected 323 males who aged from 60-92 years old in Wanshoulu area, Beijing. Luteinizint hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and total testosterone (TT) were measured by chemiluminescence technique. Free testosterone (FT), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-s) were measured by ELISA. Mean fluorescent channel (MFC) and AR% of androgen receptor in peripheral lymphocyte were analyzed by flow cytometry.Results: (1) With the ageing, serum LH, FSH and SHBG were progressively elevated, and serum TT, FT and DHEA-s level were declined, p<0.05;AR% and MFC were not changed significantly, p>0.05. (2) With increase of waist circumference, DBP and E2/T were elevated gradually. TT was descended, and E2 was ascended in obesity, p<0.05. (3) BMI (25.89±2.99 VS 24.491±2.79), waist circumference (91.750±9.61 VS 86.61±8.913) and waist-to-hip ratio (WHR) (0.906±0.053 VS 0.879±0.057) were increased in EH, p=0.000. TT (15.02±5.33 VS 17.10±6.143) was descended, and E2/T (6.94±3.89 VS 5.76±2.69) was ascended, p<0.01. With the progress of essential hypertension, BMI, waist circumference, WHR and E2/T were raised, but TT and MFC were lowered, p<0.05. Logistic regression showed that WHR (OR=7659.883), E2/T (OR-1.130) were positively correlation with EH;MFC (OR=0.729) had an inverse relationship with EH, p<0.05. (4) The waist circumference (90.75±8.38 VS 86.61±8.91), WHR (0.905±0.051 VS 0.879±0.057), SBP (140.91±20.55 VS 130.03±16.69), DBP (83.07±14.15 VS 77.21±9.34) and E2/T (7.32±3.317 VS 5.76±2.69) with peripheral arterial occlusive patients were increased significantly, p < 0.05. MFC (2.92±0.97 VS 3.36±1.05) were decreasedsignificantly, p<0.05. Logistic regression showed that E2 was positively correlation with PAOD, TT were negatively correlation with PAOD. (5) The correlation analysis showed that BMI (r=0.199, p=0.000) and E2/T (r=0.138, p=0.013) had positive relationship with history of EH, p<0.05;LH, FSH, TT were correlation with history of diabetes mellitus, p <0.05. Furthermore, BMI (r=0.1763, p=0.002) and E2/T (r=0.1366, p-0.018) were still positive relationship with history of EH;LH (r=0.1665, p=0.004) and E2/T (r=0.1195, p=0.039) were also correlation with history of diabetes mellitus after adjusting for age. But the other correlation were nor longer significant. (6) Analysis of correlation and regression: LH, FSH, TT, FT, SHBG and DHEA-s were closely correlation with the aging, p<0.05. TT (p=0.022) and E2/T (p=0.000)were correlation with SBP. E2 (p=0.002), E2/T (p=0.001), and MFC (p=0.008) were correlation with DBP. The relationship above all was still significant after adjusting for BMI. AR% was closely correlation with MFC (r=0.772, p=0.000).Conclusions: (1) With the ageing, serum LH, FSH and SHBG were progressively elevated, and TT, FT and DHEA-s level were declined. (2) TT was descended, and E2 was ascended in obesity, p<0.05. (3) BMI, waist circumference and WHR were increased in EH. TT was descended, and E2/T was ascended. With the progress of essential hypertension, BMI, waist circumference, WHR and E2/T were raised;TT and MFC were lowered. Logistic regression showed that WHR and E2/T were positively correlation with EH. MFC had an inverse relationship with EH. (4) The waist circumference, WHR, SBP, DBP and E2/T with peripheral arterial occlusive patients were increased significantly, MFC were decreased significantly. Logistic regression showed that E2 was positively correlation with PAOD, TT were negatively correlation with PAOD. (5) The correlation analysis showed that BMI and E2/T had positive relationship with history of EH;LH, FSH and TT were correlation with history of diabetes mellitus. BMI and E2/T were still positive relationship with history of EH;LH and E2/T were also correlation with history of diabetes mellitus after adjusting for age. (6) After adjusting for BMI, TT and E2/T were correlation with SBP. E2, E2/T, and MFC were correlation with DBP.Part TwoStudy of AR Gene (CAG)n Repeat Polymorphism Associated withBody fat distribution and the Level ofAndrogen in Older MenObjective: To analyze the relationship AR gene CAG length polymorphism associated with body fat distribution and the level of androgen in older men.Methods: A case control study was performed in 172 hypertension, 44 peripheral arterial occlusive diseases and 102 controls, which were randomly selected 319 males, who aged from 60-92 years old in Wanshoulu area, Beijing. Luteinizint hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and total testosterone (TT) were measured by chemiluminescence technique. Free testosterone (FT), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-s) were measured by ELISA. Mean fluorescent channel (MFC) and AR% of androgen receptor in peripheral lymphocyte were analyzed by flow cytometry. DNA obtained from peripheral leukocytes in 319 older males following phenol/trichloromethane extraction method. The CAG repeat segment from which the N-terminal domain of the first exon of the AR gene, was about 430bp amplified using polymerase chain reaction (PCR). The samples were analyzed by applied Biosystems 3730x1 DNA Analyzer.Results: (1) The AR allele length ranged from 8-35 CAG repeat in 319 older men. The most repeats were 21 (13.8%), 22 (15.7%), 23 (13.5%), and 24 (10.3%). The <20 CAG repeat people was 21%, the >25 CAG repeat people was 25.7%. Average of CAG repeat was 22.70±3.66. (2) Compared with normal controls, (CAG)n repeats were ranged from 10-33 (8-35) in essential hypertension. The most repeats were 21 (10.6% VS 17.6%), 22 (17.6% VS 14.7%), 23 (11.8% VS 15.7%), and 24 (12.4% VS 6.9%). Average of CAG repeat was 22.59±3.46 VS 22.83±3.97. So there was no significant difference in the twogroups. (3) BMI was increase gradually with CAG repeat being longer, but only significant difference in the >23 CAG repeat groups, p<0.05. Blood pressure, serum sex hormone and androgen receptor were not changed significantly with CAG repeat being longer, p> 0.05. (4) Multiple linear regression analysis showed that SBP, DBP, SHBG, E2/T were relation to body fat distribution, p<0.01. TT was negatively correlation with BMI (r=-0.204, p=0.000) and waist circumference (r=-0.182, p=0.001). E2 was only positively associated with waist circumference (r=0.129, p=0.020). CAG repeat was only positively associated with BMI (r=0.113, p=0.044). In age-adjusted partial correlations, there was no significant difference between CAG repeat and BMI (r=0.1029, p=0.067). The other correlation still existed. But LH, FSH, FT, DHEA-s, MFC and AR% were not correlation with body fat distribution. SBP, DBP, LH, FSH, TT, E2, FT, SHBG, DHEA-s, MFC and AR% were not correlation with AR CAG repeat in all men.Conclusions: (1) The AR allele length were ranged from 8-35 CAG repeat in 319 older men. Average of CAG repeats was 22.70±3.66. (2) CAG repeat was no significant difference in the two groups of essential hypertension and normal controls. (3) BMI was increase gradually with CAG repeat being longer in the >23 CAG repeat groups. (4) Multiple linear regression analysis showed that SBP, DBP, SHBG, E2/T were relation to body fat distribution. TT was negatively correlation with BMI and waist circumference. E2 was positively associated with waist circumference. Blood pressure, sex hormone, androgen receptor were not correlation with AR CAG repeat in all men. CAG repeat were only positively associated with BMI, but its association was no longer significant after adjusting for age. The other correlation still existed.
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