LOX gene polymorphisms are associated with osteoporotic vertebral compression fracture in postmenopausal Chinese women
•To explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility.•Genetic polymorphisms in LOX may contribute to susceptibility to OVCF.•The results could help identify women at higher risk of osteoporosis. Collagen cross-linking, which is regulated by lysyl oxidase (LOX), p...
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Published in | Gene Vol. 741; p. 144543 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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30.05.2020
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ISSN | 0378-1119 1879-0038 1879-0038 |
DOI | 10.1016/j.gene.2020.144543 |
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Abstract | •To explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility.•Genetic polymorphisms in LOX may contribute to susceptibility to OVCF.•The results could help identify women at higher risk of osteoporosis.
Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women.
This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures).
This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05).
The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women. |
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AbstractList | Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women.INTRODUCTIONCollagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women.This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures).METHODSThis was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures).This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05).RESULTSThis study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05).The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women.CONCLUSIONThe results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women. •To explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility.•Genetic polymorphisms in LOX may contribute to susceptibility to OVCF.•The results could help identify women at higher risk of osteoporosis. Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women. This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures). This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05). The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women. Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women.This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures).This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05).The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women. Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women. This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures). This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05). The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women. |
ArticleNumber | 144543 |
Author | He, Jinwei Zhang, Zhenlin Xiao, Wenjin Fu, Wenzhen Xu, Youjia |
Author_xml | – sequence: 1 givenname: Wenjin surname: Xiao fullname: Xiao, Wenjin organization: Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China – sequence: 2 givenname: Jinwei surname: He fullname: He, Jinwei organization: Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China – sequence: 3 givenname: Wenzhen surname: Fu fullname: Fu, Wenzhen organization: Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China – sequence: 4 givenname: Youjia surname: Xu fullname: Xu, Youjia email: xuyoujia@suda.edu.cn organization: Department of Orthopaedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China – sequence: 5 givenname: Zhenlin surname: Zhang fullname: Zhang, Zhenlin email: zhangzl@sjtu.edu.cn organization: Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China |
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CitedBy_id | crossref_primary_10_1186_s12893_023_02055_x crossref_primary_10_1016_j_xops_2022_100247 crossref_primary_10_23736_S2724_6507_21_03515_6 crossref_primary_10_3390_cancers14040981 |
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Keywords | Women CCG QTL Menopausal Lysyl oxidase DXA Cis Osteoporotic fracture OVCF Gene polymorphisms MSCs MAF LOX HWE SNPs BMD LD Chinese ZDF |
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Snippet | •To explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility.•Genetic polymorphisms in LOX may contribute to susceptibility to... Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by... |
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SubjectTerms | Absorptiometry, Photon age Aged bone density Bone Density - genetics bone fractures Chinese collagen crosslinking dual-energy X-ray absorptiometry Female femur Femur Neck - diagnostic imaging Femur Neck - physiopathology Fractures, Compression - diagnostic imaging Fractures, Compression - genetics Fractures, Compression - physiopathology Gene polymorphisms genes genetic models Genotype haplotypes hips hospitals Humans lumbar spine Lumbar Vertebrae - diagnostic imaging Lumbar Vertebrae - physiopathology Lysyl oxidase Menopausal Middle Aged osteoblasts osteoclasts Osteoporosis, Postmenopausal - diagnostic imaging Osteoporosis, Postmenopausal - genetics Osteoporosis, Postmenopausal - physiopathology Osteoporotic fracture Osteoporotic Fractures - diagnostic imaging Osteoporotic Fractures - genetics Osteoporotic Fractures - physiopathology patients postmenopause Postmenopause - genetics Postmenopause - physiology prospective studies protein-lysine 6-oxidase Protein-Lysine 6-Oxidase - genetics risk Risk Factors single nucleotide polymorphism strength (mechanics) volunteers Women X-radiation |
Title | LOX gene polymorphisms are associated with osteoporotic vertebral compression fracture in postmenopausal Chinese women |
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