| Co-Investigator(Kenkyū-buntansha) |
MIKI Tomohiro Mukogawa Women's University, School of Pharmacy and Pharmaceutical Sciences, Professor (30239206)
YASUI Naomi Mukogawa Women's University, School of Pharmacy and Pharmaceutical Sciences, Assistant (70399145)
YAMORI Yukio Mukogawa Women's University, Institute for World Health Development, Professor (80025600)
NARA Yasuo Shujistu University, Department of Biological Pharmacy, School of Pharmacy, Professor (80116417)
NOGUCHI Takanori Fukuoka Womens' University, Department of Nutrition and Health Science, Faculty of Human and Environmental Science, Associate Professor (50342829)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
We performed the screening of the candidate gene for salt-sensitive hypertension in young male normotensive Tanzanians. We evaluated the relation between angiotensin converting enzyme (ACE) insertion/deletion (VD) polymorphism and excessive salt intake. Moreover, to examine the epistatic gene-gene interaction and its effect on phenotype, we genotyped polymorphisms of the the CYP11B2 C-344T polymorphism, and examined the gene-gene interactions between ACE I/D and CYP11B2 C-344T polymorphisms in young male normotensive Tanzanians.
Two hundred male volunteers aged 25 to 35 were recruited from the Temeke District in Dar es Salaam. Informed consent for participation was obtained from all subjects. Subjects with cardiovascular diseases, renal diseases, and diabetes mellitus were excluded. Sixty-five, healthy male subjects participated in a 2-week intervention consisting of seven days of salt loading followed by diuretic treatment for a period of one week. In this protocol, subjects took 140 m
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Eq of NaC1 from consomme' and salt tablet supplements per day, and 25 mg of hydrochlorothiazide daily while maintaining their customary diet. At the baseline and on the last day of each period, blood and 24-hour urine were collected. Blood pressure (BP) was measured at the end point of each period. ACE DI polymorphism was detected by PCR.
To our knowledge, this study demonstrates for the first time the relationship between ACE gene polymorphism and salt sensitivity in Africans. Serum ACE activity in subjects with the DD genotype was significantly high compared with other genotypes after salt loading (DD; 20.2±6.9, DI; 16.4±5.2, II; 14.5±3.7 IU/L, p=0.023); however, mean blood pressure in DD, DI and II genotypes was not significantly different in the salt-loading phase.
From these results, we suggest that an interaction might exist between the ACE I/D polymorphism and ACE activity. No strong contribution was observed between blood pressure change and ACE gene polymorphism in the salt-loading phase in young male Tanzanians
To observed the interaction between the ACE I/D and the CYP11B2-C344T polymorphisms, the urinary sodium excretion in subjects with both CYPI1B2-344TC/CC and ACE DD genotypes was also notably higher than the other groups. When the CYP11B2 TC/CC genotype was present, urinary sodium excretion was significantly associated with a change of heart rate. In contrast, serum ACE activity in subjects with both CYP11B2-344TT and ACE DD genotypes was higher than in other genotype combinations. However, increases in serum ACE activity did not significantly affect blood pressure or heart rate.
Our results showed a gene-gene interaction between the ACE I/D and CYP11B2 C-344T polymorphisms in response to high salt intake, which regulates the initiation of the pressor effect of salt in essential hypertension. It provides a range of potential preventive and therapeutic approaches to hypertension. Less
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