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Inherited thrombophilia has been suggested as a cause of micro-thrombosis resulting in femoral head necrosis in Legg-Calve' Perthes Disease (LCPD). Protein C, hepatic zymogens, acts as a thrombotic agent and regulates the coagulation cascade. Genotype variations in the promoter region of the protein C gene (T-1654C; A- 1641G & A-1476T) have been reported to be associated with plasma protein C levels and thrombotic risk. In order to clarify any association of these polymorphic variations to LCPD, we analyzed the promoter region of gene for protein C (from –1704 to –1198 nt) in 70 Japanese LCPD cases (8 early-onset & 62 lateonset type) and 93 controls. Results of direct sequencing of the protein C gene promoter region showed a significantly high incidence of T-1654C change in early-onset LCPD cases than among the late-onset LCPD and control groups. Our results, therefore, suggest a significant association between early onset LCPD and the T-1654C mutation in the protein C promoter region. Key Words: Protein C gene promoter region polymorphism, micro thrombosis, early-onset LCPD.

SIGNIFICANTLY HIGH INCIDENCE OF T-1654C POLYMORPHIC VARIATION IN THE PROTEIN C GENE PROMOTER REGION IN EARLY ONSET LEGG-CALVE' PERTHES DISEASE