The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women.
The objective was to identify single nucleotide polymorphisms (SNPs) in exons of the osteoprotegerin gene and to analyze the relationship between the SNPs and bone mineral density in postmenopausal women. We used polymerase chain reaction (PCR) and direct sequencing methods to identify SNPs and genotypes in 205 postmenopausal women. BMD at the lumbar spine (L2-4) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry (DEXA). Serum osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL) and urinary N-telopeptide of type I collagen (NTx) were also measured. In exon 1 of the OPG gene, we found the Lys3Asn SNP. In 205 postmenopausal women, the Asn-allele frequency was 26.0%, and the distribution of Lys3Asn genotypes was Lys-Lys 56.6%, Lys-Asn 34.6% and Asn-Asn 8.8%, respectively. BMD at the lumbar spine (L2-4) of the Asn-Asn genotype was significantly higher (9.5-12.6%) than Lys-Asn and Lys-Lys genotypes (P=0.012), with evidence for an allele dose effect (P=0.008). Results remained similar after adjustment for age and body mass index. The Lys3Asn polymorphism of the OPG gene alone accounted for 7.7% of the variance of the L2-4 BMD in a multiple regression model. Logistic regression analysis revealed that the OPG genotype Lys-Lys had a 2.7 times (95% CI: 0.83-9.11) greater risk for osteopenia/osteoporosis than the Asn-Asn genotype. The Lys3Asn polymorphism in the OPG gene is associated with L2-4 BMD in postmenopausal women. The Lys-allele is associated with lower BMD and an increased risk for osteoporosis.
Zhao
Hong-yan
HY
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University, 197 Ruijin Er Road, 200025, Shanghai, China.
Liu
Jian-min
JM
Ning
Guang
G
Zhao
Yong-ju
YJ
Zhang
Lian-zhen
LZ
Sun
Li-hao
LH
Xu
Man-yin
MY
Uitterlinden
A G
AG
Chen
Jia-lun
JL
D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D001851:Bone Diseases, Metabolic / Q000235:genetics; D002352:Carrier Proteins / Q000097:blood; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D005091:Exons; D005260:Female; D005272:Femur Neck; D005787:Gene Frequency; D005838:Genotype; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D008159:Lumbar Vertebrae; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D053244:Osteoprotegerin; D010455:Peptides / Q000652:urine; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*
D002352:Carrier Proteins; D024042:Collagen Type I; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen