Abstract-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II.Human angiotensinogen gene contains a C/A polymorphism at Ϫ20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at Ϫ20, this sequence binds to the estrogen receptor.We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at Ϫ20 is increased on cotransfection of an expression vector containing human estrogen receptor-␣ coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at Ϫ20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at Ϫ20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at Ϫ20. Our data suggest that C/A polymorphism at Ϫ20 may modulate the expression of human angiotensinogen gene in a sex-specific manner. (Hypertension. 1999;33:108-115.)Key Words: angiotensinogen Ⅲ genes Ⅲ polymorphism Ⅲ estrogen Ⅲ gene regulation Ⅲ regulation, hormonal Ⅲ major late transcription factor T he renin-angiotensin system plays an important role in the regulation of blood pressure, fluid balance, and electrolyte homeostasis. Angiotensin II, which is 1 of the most potent vasoactive hormones, is obtained from its precursor molecule, angiotensinogen, by the combined proteolytic action of renin and angiotensin-converting enzyme. Angiotensinogen is primarily synthesized in the liver, although recent studies have shown that its mRNA is also present in fat, brain, kidney, heart, and aorta of rats 1 and humans.2 Because plasma concentration of angiotensinogen is close to the Michaelis constant of the enzymatic reaction between renin and angiotensinogen, 3 a rise or fall in plasma angiotensinogen levels can lead to a parallel change in the formation of angiotensin II, and an increase in plasma angiotensin II may lead to hypertension. Previous studies have shown a highly significant correlation between plasma concentrations of angiotensinogen and blood pressure, 4 higher plasma angiotensinogen concentrations in hypertensive parents and their offspring, 5 and elevations of blood pressure in transgenic animals overexpressing the angiotensinogen gene. 6,7 Recent studies have suggested that the angiotensinogen gene locus is involved in human essential hypertension 8 and pregnancy-induced hypertension. 9Human angiotensinogen gene contains a C/A polymorphism at Ϫ20 located between the TATA box and transcriptional initiation site. 8 We show here that this region of the promoter binds to estrogen receptor-␣ when nucleoside A is present at Ϫ20. We also show that a reporter construct, pHAG1.2CAT (Ϫ20A), is transactivated by cotransfection of the mammalian expression vector pSG5 containing th...

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Background and Objectives: Allergy to house dust mite is one of the most common causes of allergic rhinitis (AR) in China. We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR. Methods: The trial was a prospective and randomized study involving 96 patients with persistent AR, aged 14–60 years, who were allergic to Dermatophagoides pteronyssinus. While 48 patients were randomly assigned to the cluster schedule reaching the maintenance dose within 6 weeks, the other 48 were randomly assigned to the conventional schedule reaching the maintenance dose within 14 weeks. Eighty-nine patients completed a 1-year treatment course. While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment, quality of life, cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment. Results: The cluster schedule reduced the time to reach the maintenance dose by 57% and caused mild systemic adverse reactions after 1.0% of injections (6.7% of patients), with no differences in comparison with the conventional schedule. Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule. Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year. Conclusions: The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner.

Objective: Obesity-related disease risks may vary depending on whether the subject has metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO). At least 5 definitions/criteria of obesity and metabolic disorders have been documented in the literature, yielding uncertainties in a reliable international comparison of obesity phenotype prevalence. This report aims to compare differences in MHO and MUO prevalence according to the 5 most frequently used definitions. Methods: A random sample of 4,757 adults aged 35 years and older (male 51.1%) was enrolled. Obesity was defined either according to body mass index or waist circumference, and the definitions of metabolic abnormalities were derived from 5 different criteria. Results: In MHO, the highest prevalence was obtained when using the homeostasis model assessment (HOMA) criteria (13.6%), followed by the Chinese Diabetes Society (11.4%), Adult Treatment Panel III (10.3%), Wildman (5.2%), and Karelis (4.2%) criteria; however, the MUO prevalence had an opposite trend to MHO prevalence. The magnitude of differences in the age-specific prevalence of MHO and MUO varied greatly and ranked in different orders. The proportion of insulin resistance for MHO and MUO individuals differed significantly regardless of which metabolic criterion was used. Conclusion: The prevalence of MHO and MUO in the Chinese population varies according to different definitions of obesity and metabolic disorders.