The LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass and point to Dkk as a potential target for the prevention or treatment of osteoporosis.

A study of coronary heart disease (CHD) among Japanese migrants compared with Japanese living in Japan provided the opportunity to study factors possibly responsible for the high rates of CHD in America as compared with Japan. Comparable methods were employed in examining 11,900 men of Japanese ancestry aged 45--69 living in Japan, Hawaii and California. The age-adjusted prevalence rates for definite CHD as determined by ECG were: Japan 5.3, Hawaii 5.2 and California 10.8/1000. For definite plus possible CHD the rates were 25.4, 34.7 and 44.6. The prevalence of angina pectoris and pain of possible myocardial infarction, determined by questionnaire, showed a similar gradient. Elevated serum cholesterol showed a Japan-Hawaii-California gradient, but the prevalence of hypertension in Japan was intermediate between the prevalence in Hawaii and the higher prevalence in California. The three geographic locations were compared as to prevalence of CHD at comparable levels of blood pressure and cholesterol. At each blood pressure level and at each cholesterol level, the greater prevalence of CHD in California persisted. These facts, plus the near universality of smoking in Japan, suggest that conventional risk factors only partly explain the observed gradient in CHD.

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