Hypothesis: Cystic fibrosis carrier geography reflects interactions of tuberculosis and hypertension with vitamin D deficiency, altitude and temperature. Vitamin D deficiency effects and CF carrier advantage.

Interactions between selective factors (hypertension and tuberculosis) and environmental effects (vitamin D deficiency [VDD], temperature, and altitude) largely explain cystic fibrosis (CF) carrier geography. For VDD sequelae such as hypertension and tuberculosis vulnerability, clinical evidence of carrier protection is supported by indications that decreased CF arylsulfatase B activity suppresses tuberculosis, and that excess CF salt loss decreases blood pressure. A need for salt retention in the tropics selected against CF carriers despite possible advantages against cholera, typhoid, and other factors, but salt retention was less important elsewhere. Increased hypertension with cold selected for carriers with increasing latitude, and with altitude, where hypertensive complications of pregnancy also rise. ΔF508 rates especially seem to follow these parameters, and may be particularly protective against hypertension, while lower rates in Ashkenazi Jews are consistent with a greater role for tuberculosis in this group. This scenario suggests geographical correlations of CF with other genes affecting blood pressure, and significant carrier levels, especially of ΔF508, in mountainous areas of Asia with VDD.