Abstract
Osteoporosis and osteoporotic fractures are strongly associated with mortality and morbidity, both in developing and developed countries. Menopause accelerates bone loss due to estrogen deficiency and age-related linear bone loss. We investigated plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in postmenopausal women with osteoporotic vertebral compression fractures (OVCFs). In this case-control study, 355 postmenopausal women were genotyped for the presence of PAI-1 gene polymorphisms −844A > G, −675 4G > 5G, 43G > A, 9785A > G, and 11053T > G. Genetic polymorphisms of PAI-1 were analyzed by the polymerization chain reaction restriction fragment length polymorphism assay, and their association with disease status and folate and homocysteine levels was determined in 158 OVCF patients and 197 control subjects. The PAI-1 −675 5G5G (adjusted odds ratio (AOR), 3.302; p = 0.017) and 43GA + AA (AOR, 2.087; p = 0.042) genotype frequencies showed significant association with the increased prevalence of OVCFs in postmenopausal women. In addition, we performed gene–environment interaction studies and demonstrated an association between PAI-1 gene polymorphisms and OVCF prevalence. Our novel finding is the identification of several PAI-1 genetic variants that increase susceptibility to OVCF. Our findings suggest that polymorphisms in PAI-1 may contribute to OVCF, and that they can be developed as biomarkers for evaluating OVCF risk.
Highlights
Osteoporosis is a common metabolic bone disorder characterized by reduced bone mass, increased skeletal fragility, microarchitectural deterioration, and an increase in bone fractures [1]
It shows a significant correlation between osteoporotic vertebral compression fracture (OVCF) risk and plasminogen activator inhibitor-1 (PAI-1) polymorphisms, −844G > A (GG vs. GA: adjusted odds ratio (AOR) 2.244, 95% confidence interval (CI) 1.164–4.326, p = 0.015; GG vs. GA + AA: AOR 1.918, 95% CI 1.016–3.621, p = 0.044), −675 4G > 5G (4G4G vs. 5G5G: AOR 4.646, 95% CI 1.625–13.286, p = 0.004; 4G4G vs. 4G5G + 5G5G: AOR 1.969, 95% CI 1.130–3.430, p = 0.017; 4G4G + 4G5G vs. 5G5G: AOR 3.378, 95% CI 1.301–8.769, p = 0.012), and +43 G > A (GG vs. GA: AOR 2.421, 95% CI 1.057–5.546, p = 0.017; GG vs. GA + AA: AOR 2.292, 95% CI 1.009–5.206, p = 0.048)
We found an association between PAI-1 polymorphisms and osteoporosis risk in postmenopausal women
Summary
Osteoporosis is a common metabolic bone disorder characterized by reduced bone mass, increased skeletal fragility, microarchitectural deterioration, and an increase in bone fractures [1]. Osteoporosis leads to decreased skeletal strength and increased fracture susceptibility. Osteoporotic fractures are a leading cause of disability and, subsequently, death in postmenopausal women [1,2]. The occurrence of osteoporotic fractures is closely associated with mortality worldwide [3,4]. Osteoporosis and osteoporotic fractures occur frequently in postmenopausal women due to decreased estrogen levels [5,6]. Estrogen deficiency associated with menopause, combined with age-related linear bone loss, leads to accelerated bone loss [7]. A previous study has shown that several gene polymorphisms can affect BMD levels [6,12,13,14,15,16]
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