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Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women.
Bone. 2007 Apr; 40(4):997-1005.BONE

Abstract

Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of Wnt signaling, is an important regulator of bone development and maintenance. Recently we identified correlation between an intronic single-nucleotide polymorphism (SNP) in the LRP5 gene and vertebral bone mineral density (BMD), indicating that a genetic ground exists at this locus for determination of BMD. In the study reported here, we searched for nucleotide variation(s) that might confer susceptibility to osteoporosis among an extended panel of 387 healthy subjects recruited from the same hospital (Group-A), as well as among 384 subjects from the general population in eastern Japan (Group-B). We basically focused on two potentially functional variations, Q89R (c.266A > G) and A1330V (c.3989C > T), whose functional effects by the amino-acid changes were estimated by the SIFT software program; it predicted the 1330 V allele as deleterious ("intolerant") although the minor allele of Q89R was questionable. By analyzing associations between the variant alleles and the BMD, reproducible association of the minor variant of A1330V to lower adjusted BMD levels was detected; i.e., In Group-A subjects 1330-V significantly associated with the spinal BMD Z-score (P = 0.034), and in Group-B it associated with low radial BMD (P = 0.019). From haplotype and linkage disequilibrium (LD) analysis for 29 SNPs, we detected two separate LD blocks within the entire 137-kb LRP5 locus, basically consistent with a previous report on Caucasians. One of the second block haplotype significantly associated with adjusted BMD (r = 0.15, P = 0.004). Possible combined effect of Q89R and A1330V belonging to different LD blocks was denied by multiple regression analyses. Our results indicate that genetic variations in LRP5 are important factors affecting BMD in adult women and that 1330 V may contribute to osteoporosis susceptibility, at least in Japanese.

Authors+Show Affiliations

Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan. ezura.mph@mri.tmd.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17306638

Citation

Ezura, Yoichi, et al. "Association of a Single-nucleotide Variation (A1330V) in the Low-density Lipoprotein Receptor-related Protein 5 Gene (LRP5) With Bone Mineral Density in Adult Japanese Women." Bone, vol. 40, no. 4, 2007, pp. 997-1005.
Ezura Y, Nakajima T, Urano T, et al. Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone. 2007;40(4):997-1005.
Ezura, Y., Nakajima, T., Urano, T., Sudo, Y., Kajita, M., Yoshida, H., Suzuki, T., Hosoi, T., Inoue, S., Shiraki, M., & Emi, M. (2007). Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone, 40(4), 997-1005.
Ezura Y, et al. Association of a Single-nucleotide Variation (A1330V) in the Low-density Lipoprotein Receptor-related Protein 5 Gene (LRP5) With Bone Mineral Density in Adult Japanese Women. Bone. 2007;40(4):997-1005. PubMed PMID: 17306638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. AU - Ezura,Yoichi, AU - Nakajima,Toshiaki, AU - Urano,Tomohiko, AU - Sudo,Yoshihiro, AU - Kajita,Mitsuko, AU - Yoshida,Hideyo, AU - Suzuki,Takao, AU - Hosoi,Takayuki, AU - Inoue,Satoshi, AU - Shiraki,Masataka, AU - Emi,Mitsuru, Y1 - 2007/02/15/ PY - 2004/10/20/received PY - 2005/05/29/revised PY - 2005/06/13/accepted PY - 2007/2/20/pubmed PY - 2007/6/8/medline PY - 2007/2/20/entrez SP - 997 EP - 1005 JF - Bone JO - Bone VL - 40 IS - 4 N2 - Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of Wnt signaling, is an important regulator of bone development and maintenance. Recently we identified correlation between an intronic single-nucleotide polymorphism (SNP) in the LRP5 gene and vertebral bone mineral density (BMD), indicating that a genetic ground exists at this locus for determination of BMD. In the study reported here, we searched for nucleotide variation(s) that might confer susceptibility to osteoporosis among an extended panel of 387 healthy subjects recruited from the same hospital (Group-A), as well as among 384 subjects from the general population in eastern Japan (Group-B). We basically focused on two potentially functional variations, Q89R (c.266A > G) and A1330V (c.3989C > T), whose functional effects by the amino-acid changes were estimated by the SIFT software program; it predicted the 1330 V allele as deleterious ("intolerant") although the minor allele of Q89R was questionable. By analyzing associations between the variant alleles and the BMD, reproducible association of the minor variant of A1330V to lower adjusted BMD levels was detected; i.e., In Group-A subjects 1330-V significantly associated with the spinal BMD Z-score (P = 0.034), and in Group-B it associated with low radial BMD (P = 0.019). From haplotype and linkage disequilibrium (LD) analysis for 29 SNPs, we detected two separate LD blocks within the entire 137-kb LRP5 locus, basically consistent with a previous report on Caucasians. One of the second block haplotype significantly associated with adjusted BMD (r = 0.15, P = 0.004). Possible combined effect of Q89R and A1330V belonging to different LD blocks was denied by multiple regression analyses. Our results indicate that genetic variations in LRP5 are important factors affecting BMD in adult women and that 1330 V may contribute to osteoporosis susceptibility, at least in Japanese. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/17306638/Association_of_a_single_nucleotide_variation__A1330V__in_the_low_density_lipoprotein_receptor_related_protein_5_gene__LRP5__with_bone_mineral_density_in_adult_Japanese_women_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(05)00275-9 DB - PRIME DP - Unbound Medicine ER -