| Project/Area Number |
10671040
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | UNIVERSITY OF THE RYUKYUS |
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Principal Investigator |
KOMIYA Ichiro UNIV OF THE RYUKYUS, MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (50162061)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMABUKURO Michio UNIV OF THE RYUKYUS, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (60271144)
YOSHIDA Hisashi UNIV OF THE RYUKYUS, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (50210711)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | HYPERTENSION, ESSENTIAL / ALDOSTERONE / CYTOCHROME P-450 / POLYMORPHISM / RENIN-ANGIPTENSIN SYSTEM |
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| Research Abstract |
We analyzed the association of 2 biallelic polymorphisms of CYP11B2 (P450c11AS) gene, one in the Lys^<173> Arg of exon 3 and other in the promoter at position -344T/C, with hypertension in 73 hypertensive patients and 134 normotensive subjects. The association between low-renin hypertension and angiotensin-I converting enzyme (ACE) gene was also analyzed. An elevated ratio of plasma aldosterone concentration to plasma renin activity (PAC : PRA) was used to identify low-renin hypertension. Genotypes for CYP11B2 and ACE were determined by polymerase chain reactions.
The Arg^<173> allele frequency did not differ between hypertensive patients considered as one group (34%) and normotensive controls (37%). However, only 22% of 58 CYP11B2 alleles studied in 29 patients with low-renin hypertension were Arg^<173> alleles, while frequency of this allele was 41% in patients with a normal- or high-renin hypertension (P=0.033). Analysis of the distribution of -344C and Arg^<173> genotypes indicated
… More
that these two variants were in complete linkage disequilibrium : -344C was present in a subset of chromosomes carrying the Arg^<173> (P<0.001 in low-renin hypertension). So, the frequency of the -344C allele was low in the patients with low-renin hypertension, compared with those with a normal-or high-renin hypertension. Deletion (D) allele frequencies of the ACE gene were 31% in the patients with low-renin hypertension, 39% in the patients with normal-or high-renin hypertension, and 29 % in normotensive controls.
We detected an association between the CYP11B2 gene polymorphisms and low-renin hypertension with inappropriate elevation of aldosterone. The decreased frequencies of the Arg^<173> and -344C variants in the CYP11B2 appear to be genetically linked to low-renin hypertension in the Japanese population studied. We are analyzing other genes, such as angiotensinogen, angiotensin II type 2 receptor, G-protein subunit, and α-adducin. We are also investigating the enzyme function of the phenotype Lys^<173> and -344T using transfected cell. Less
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