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.8762 G>A; (Arg325Gln). When the kinetic parameters of GGCX325-Gln and GGCX325-Arg were compared in vitro, Vmax/Km was significantly higher for GGCX325-Gln (944.4+/-9.21 pmol/30 min/mg/mM FLEEL) than for GGCX325-Arg (671.9+10.79 pmol/30 min/mg/mM FLEEL) (p=0.018). Then, association study of this polymorphism with forearm bone mineral density (BMD) of Japanese postmenopausal women (n=500, age 73.6+/-5.74) was conducted. As a result, the body mass index (BMI)-adjusted Z score in the subpopulation older than 75 years (n=207) was higher in those with 325-Gln (0.650+/-0.883, mean+/-SD) than those with 325-Arg/Gln or 325-Arg (0.133+/-0.650) (p=0.0383). This is the first report to demonstrate the different activities of GGCX between the common genotypes and their association with BMD.
Kinoshita
Hiroyuki
H
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Nakagawa
Kimie
K
Narusawa
Ken'ichiro
K
Goseki-Sone
Masae
M
Fukushi-Irie
Mariko
M
Mizoi
Lena
L
Yoshida
Hideyo
H
Okano
Toshio
T
Nakamura
Toshitaka
T
Suzuki
Takao
T
Inoue
Satoshi
S
Orimo
Hajime
H
Ouchi
Yasuyoshi
Y
Hosoi
Takayuki
T
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D044466:Asian People; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D019556:COS Cells; D019735:Carbon-Carbon Ligases / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D020641:Polymorphism, Single Nucleotide; D014812:Vitamin K / Q000502:physiology*
D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase