Studies on congenital protein C deficiency in Japanese: Prevalence, genetic analysis, and relevance to the onset of arterial occlusive diseases

Hereditary protein C deficiency is associated with a predisposition to veno us thrombosis. We identified 43 patients with protein C deficiency by scree ning approximately 26,800 patients admitted to the National Cardiovascular Center Hospital. The observed prevalence of protein C deficiency was 1 per 620. We performed genetic analyses of 57 Japanese families with protein C d eficiency. Combined with the results of the other studies in 10 families, t he 67 Japanese families with protein C deficiency have been examined and 39 different gene defects have been identified. Some changes were solely iden tified in Japanese subjects, whereas others showed no such ethnic bias. The recurrent defects of Phe139Val, Arg169Trp, Val297Met, and Met364Ile substi tutions and a G8857 deletion were found in 33 Japanese families, accounting for 49% of Japanese families with protein C deficiency, Finally, we examin ed the relevance of protein C deficiency to the onset of arterial occlusive diseases. In the examination of whether protein C deficiency hastens arter ial occlusion, we found a significant difference (p = 0.02) in the age at o nset of acute myocardial infarction between the patients with protein C def iciency (n = 10: 49.4 +/- 14.8 years) and a group of patients with normal p rotein C levels (n = 42: 60.5 +/- 10.6 years). At the onset of atherothromb otic cerebral infarction, the patients with protein C deficiency were signi ficantly (p 0.022) younger (n = 11:57.4 +/- 12.8 years) than those with nor mal protein C levels (n = 48: 64.6 +/- 10.1 years). Thus, we conclude that congenital protein C deficiency hastens the onset of arterial occlusive dis eases, especially acute myocardial infarction, in Japanese subjects.