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 inGene Vol. 741; p. 144543
Main Authors Xiao, Wenjin, He, Jinwei, Fu, Wenzhen, Xu, Youjia, Zhang, Zhenlin
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 30.05.2020
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ISSN0378-1119
1879-0038
1879-0038
DOI10.1016/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.
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
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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
Language English
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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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StartPage 144543
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
URI https://dx.doi.org/10.1016/j.gene.2020.144543
https://www.ncbi.nlm.nih.gov/pubmed/32165300
https://www.proquest.com/docview/2377343508
https://www.proquest.com/docview/2511182217
Volume 741
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