Risk factor effects and total mortality in older Japanese men in Japan and Hawaii.

PURPOSE: We sought to identify factors related to total mortality in older Japanese men in Japan and Hawaii. METHODS: Baseline data were collected from 1980 to 1982 in 1379 men in Hawaii and 954 men in Japan. Ages ranged from 61 to 81 years, with mortality follow-up during a 19-year period. RESULTS: Compared with Japan, men in Hawaii had a 2-fold excess of diabetes and a 4-fold excess of prevalent coronary heart disease (P < .001). Total cholesterol and body mass index were also greater in Hawaiian men (P < .001). In contrast, men in Japan had greater systolic blood pressure and were nearly 3 times more likely to smoke cigarettes (P < .001). Although each cohort had elements of a poor risk factor profile, there was a 1.4-fold excess in the risk of death in Japan (49.4 vs. 36.2/1,000 person-years, P < .001). Although mortality was similar after risk factor adjustment, only blood pressure and cigarette smoking accounted for the higher risk of death in Japan. CONCLUSIONS: Cigarette smoking and hypertension explain much of the excess mortality in Japan versus Hawaii. In this comparison of genetically similar cohorts, evidence further suggests that Japanese in Japan are equally susceptible to develop the same adverse risk factor conditions that exist in Hawaii.

Mutations in the vasopressin V2 receptor gene in families with nephrogenic diabetes insipidus and functional expression of the Q-2 mutant.

Nephrogenic diabetes insipidus (NDI) is characterized by a resistance of the kidney towards arginine vasopressin (AVP). Following molecular cloning of the vasopressin V2 receptor, we identified different mutations in the V2 receptor gene in families with X-linked NDI, which segregated with the disease. The Hopewell mutation (W71X) causes the disease in the largest North American NDI pedigree, with most of its members residing on Nova Scotia. Different mutations were found in three families from the Quebec area (Q-2: R137H, Q-3: R113W, Q-5: 804delG) and in the large Cannon kindred residing in Utah (L312X). In an Iranian family (O-1), another mutation was detected (A132D). Three of the six mutations (Hopewell, Cannon, Q-5) are predicted to cause the expression of a truncated V2 receptor and are therefore unlikely to function. The functional consequences of missense mutations (Q-2, Q-3, O-1) are less obvious. We therefore introduced the Q-2 mutation into wild-type cDNA. When expressed in COS.M6 or Ltk cells, the Q-2 mutant bound AVP with normal affinity. However, cells expressing the Q-2 mutant failed to respond to AVP with an increase in adenylyl cyclase activity. Thus the Q-2 mutant is unable to interact with or to activate the stimulatory G-protein Gs. The present data indicate that X-linked NDI is frequently attributable to a mutation in the V2 receptor gene. In addition, the data prove biochemically that the Q-2 mutation is the cause of NDI in the Q-2 family.