Predispositions to essential hypertension and cardiovascular diseases are possibly associated with gene polymorphisms of the renin-angiotensin system. Gene polymorphisms of angiotensinogen and angiotensinconverting enzyme genes have been suggested to be risk factors for hypertension and myocardial infarction. Concerning the polymorphism of aldosterone synthase (CYP11B2) gene, earlier studies have shown inconsistent results in terms of its relation to hypertension. In the present case-control study, we investigated the association of À344T/C polymorphism in the promoter region of human CYP11B2 gene with genetic predisposition to hypertension. The genotype of À344T/C polymorphism was determined in essential hypertension subjects (n ¼ 250) and normotensive subjects (n ¼ 221). The distributions of three genotypes (TT, TC, and CC) were significantly different between the hypertensive and the normotensive groups (v 2 ¼ 9.61, P ¼ 0.008). Namely, the frequency of C allele was higher in the hypertensive patients than in the normotensive subjects (34.2 vs 26.5%, P ¼ 0.010). Our data suggest that the À344C allele of CYP11B2 gene polymorphism is associated with the genetic predisposition to develop essential hypertension.

Abstract-Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human AM gene and have determined that the gene is located in the short arm of chromosome 11. The 3Ј-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to hypertension. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57Ϯ5 years and 266 patients with essential hypertension (EH) age 53Ϯ11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117Ϯ13/73Ϯ9 mm Hg in NT and 170Ϯ23/104Ϯ12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH ( 2 ϭ9.43, Pϭ0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT ( 2 ϭ7.62, Pϭ0.007). In NT, plasma AM concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes. Key Words: adrenomedullin Ⅲ polymorphism Ⅲ hypertension, essential Ⅲ microsatellite repeats Ⅲ genetics A drenomedullin (AM) is a hypotensive peptide produced in cardiovascular tissues such as the heart, lung, kidney, and vascular wall. 1,2 Besides the potent vasodilator action, AM has also been shown to cause natriuresis in the kidney and to inhibit growth of cardiovascular cells. Moreover, a significant level of AM has been identified in human plasma, and AM is supposed to be a circulating hormone. 1,3 We have previously reported that plasma AM levels are increased in patients with cardiovascular diseases such as hypertension, renal failure, and heart failure. 4,5 These findings suggest that AM has implications in pathophysiology of the cardiovascular system.We have cloned and sequenced the genomic DNAencoding human AM gene and have determined that the gene is located in the short arm of chromosome 11. 6 Nucleotide sequencing of genomic DNA adjacent to the AM gene revealed that the 3Ј-end of the gene is flanked by the microsatellite marker with a variable number of cytosine adenine (CA)-repeats. This microsatellite marker is located approximately 4 kb downstream of the AM gene. Considering the possible implications of AM in the cardiovascular system, it seems of interest to elucidate whether this gene variation has any relation to the etiology of cardiovascular diseases. In the present study, we investigated the relationship between the microsatellite polymorphism adjacent to the AM gene and genetic predisposition to essential hypertension. Subjects and Methods Study SubjectsA group...

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The present study tested the effects of valsartan, an angiotensin II receptor blocker, on the progression of renal insufficiency in patients with nondiabetic renal diseases. The study subjects were 22 patients with nondiabetic renal diseases whose serum creatinine (Cr) ranged from 1.