|Budget Amount *help
¥6,900,000 (Direct Cost : ¥6,900,000)
Fiscal Year 1996 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1995 : ¥4,300,000 (Direct Cost : ¥4,300,000)
Essential hypertension is generally agreed to be multifactorial disease. In susceptible individuals, it is likely that environmental factors interact with multiple genetic determinants to produce high blood pressure. Identifying the responsible genes would not only provide clues about the mechanisms of the regulation of blood pressure, but also enable identification of subjects at genetically high risk for hypertension for whom preventive measures could then be taken. We have previously shown that in Japanese, the frequency of TT genotype of angiotensinogen M235T variant is significantly high in hypertensives when compared with normotensives.
Subjects of the present study were residents of Takasu, which locates nearby Asahikawa, Hokkaido, who underwent annual multiphasic health checkups. 130 cases of hypertensive men and 146 age matched male normotensives were chosen on the basis of clinical data. Three variants of angiotensinogen gene, which are M235T,A-20G,and A-6G,I/D variant of angiotensin-converting enzyme gene, A1166C variant of angiotensin II type 1 receptor gene, and Q192R variant of paraoxonase gene were genotyped. The frequencies of TT genotype of M235T and AA genotype of A-6G were significantly high is hypertensives when compared with normotensives. In addition, we found that the A-6G variant was almost completely linked (more than 99%) to the M235T variant. With the fact that individuals with TT genotype have higher plasma angiotensinogen level, we might be able to say that A-6G is the responsible mutation for essential hypertension by increased promoter activity and M235T is the linked genetic marker.