A functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women.

The vitamin-K-dependent gamma-glutamyl carboxylase (GGCX) carboxylates vitamin-K-dependent proteins including bone Gla protein (osteocalcin) and matrix Gla protein, which play important roles in bone metabolism. Therefore, GGCX polymorphism might explain in part individual susceptibility to osteoporosis. In the present study, polymorphisms in the exons of this gene were screened in Japanese elderly women and a non-synonymous single nucleotide polymorphisms (SNP) were found; c.

Functional analysis of the single nucleotide polymorphism (787T>C) in the tissue-nonspecific alkaline phosphatase gene associated with BMD.

Unlabelled: Polymorphisms of the TNSALP gene have not previously been studied as a possible determinant for variations in BMD or as a predisposing genetic factor for osteoporosis. This study showed a significantly higher association between the 787T>C (Tyr246His) TNSALP gene and BMD among 501 postmenopausal women. Furthermore, the effects of amino acid substitution on the catalytic property of the protein translated from the 787T>C gene were examined.

The mutant (F310L and V365I) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia.

Hypophosphatasia (HOPS) is a heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity and premature loss of deciduous teeth. In a previous study, we detected missense mutations in the TNSALP gene of a patient who inherited the F310L and the V365I mutation with severe periodontitis and childhood HOPS. Expression of the mutant V365I TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant had undetectable ALP activity.