LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.
Osteoporosis is a multifactorial trait with low bone mineral density (BMD). We report results of an association study between BMD and nine candidate genes ( TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis. Samples for the former association study included 481 general Japanese women. Among the nine candidate genes examined, only LRP5 showed a significant association with BMD. We identified a strong linkage disequilibrium (LD) block within LRP5. Of five LPR5 single nucleotide polymorphisms (SNPs) that are located in the LD block, three gave relatively significant results: Women with the C/C genotype at the c.2220C>T SNP site had higher adjusted BMD (AdjBMD) value compared to those with C/T and T/T (p=0.022); and likewise, G/G at IVS17-30G>A and C/C women at c.3989C>T showed higher AdjBMD than those with G/A or A/A (p=0.039) and with C/T or T/T ( p=0.053), respectively. The case-control study in another series of samples consisting of 126 osteoporotic patients and 131 normal controls also gave a significant difference in allele frequency at c.2220C>T (kappa2=6.737, p=0.009). These results suggest that LRP5 is a BMD determinant and also contributes to a risk of osteoporosis.
Mizuguchi
Takeshi
T
Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.
Furuta
Itsuko
I
Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Watanabe
Yukio
Y
Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.|Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.
Tsukamoto
Kazuhiro
K
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.|Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Tomita
Hiroshi
H
Nagasaki Prefectural Medical Health Center, Nagasaki, Japan.
Tsujihata
Mitsuhiro
M
Nagasaki Kita Hospital, Nagasaki, Japan.
Ohta
Tohru
T
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.|Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
Kishino
Tatsuya
T
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.|Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
Matsumoto
Naomichi
N
Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.
Minakami
Hisanori
H
Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Niikawa
Norio
N
Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan.
Yoshiura
Koh-Ichiro
KI
Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. kyoshi@net.nagasaki-u.ac.jp.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Japan. kyoshi@net.nagasaki-u.ac.jp.
D001483:Base Sequence; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D026502:LDL-Receptor Related Proteins; D015810:Linkage Disequilibrium; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology*; D017422:Sequence Analysis, DNA
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011973:Receptors, LDL