Study On The Genetic Association Of LRP5 And VDR Gene Polymorphism And Susceptibility To Osteoporosis In Patients With Chronic Obstructive Pulmonary Disease

Objective Osteoporosis is a common comorbidity of chronic obstructive pulmonary disease?COPD?.Fracture caused by osteoporosis seriously affects the prognosis of COPD patients.To understantd the genetics mechanism of osteoporosis in COPD,the associations between LRP5 and VDR gene polymorphisms and susceptibility of osteoporosis in patients with COPD were investigated.Through analying the correlation between computed tomography?CT?value of thoracolumbar vertebrae and bone mineral density.The threshold CT value of vertebral body for osteoporosis was selected,and then patients were grouped according to the CT threshold..Methods First of all,86 patients with acute exacerbation of COPD were included in this study.All these patients received chest CT scan and DXA examination within one month after admission.The relation between each CT value from 6^ththoracic vertebrae?T6?to 1^stlumbar?L1?and T-score measured by DXA was analyzed by linear correlation analysis.We calculated the threshold CT value of vertebral body for osteoporosis.Secondly,based on this threshold CT value,380 patients?including the86 patients in the first part?with acute exacerbation of COPD were divided into groups of non osteoporosis and osteoporosis.Genomic DNA was extracted from all patients.Then genetic association was analysed.UCSC genome browser and haploview4.2 software were used to screen tagSNP of LRP5 gene and VDR gene.The tagSNPs in LRP5 and VDR genes were selected by Sequenom MassARRAY SNP detection methods.T test,chi-square test and logistic regression were used to analyse the OR values and confidence intervals of each SNP in the codominant,dominant and recessive genetic models.To assess the association between single nucleotide polymorphisms in LRP5 and VDR genes and osteoporosis in COPD patients.Results The CT values of T6-L1 were positively correlated with T-score?r=0.517,0.497,0.463,0.508,0.471,0.425,0.445,0.523,respectively,all P value<0.001?.The ROC curve analysis showed that the area under ROC curve of L1 CT value was the largest?0.702?,therefore the accuracy of diagnosis of osteoporosis by L1 CT value was better.L1 CT value lower than 100 HU suggests patients with lower bone mass or osteoporosis.According to L1-CT value,380 COPD patients were divided into two groups.In the group of COPD with osteoporosis,there were more females,elder,higher peripheral platelet counts,hypophosphaemia and lower serum creatinine ?P<0.05?.By genetic association study,rs901823 of LRP5 gene carrying C/C genotype had a higher risk of osteoporosis than carrying T/T and C/T genotype in COPD patients?in recessive mode:C/Cvs.T/T+C/T,OR=9.42,95%CI=2.01-44.29,P=0.0004318?,rs2853561 of VDR gene carrying T/C and T/T genotype had a lower risk of osteoporosis than those carrying C/C genotype in COPD patients?in dominant mode:T/C+T/Tvs.C/C,OR=0.34,95%CI=0.18-0.63,P=0.0003539?,The differences were statistical significance.Conclusion This study indicates that there is a positively correlation between vertebral body CT and bone mineral density in COPD patients.In clinical work,the CT value of vertebral body can be used to screen patients of COPD with osteoporosis.The study of gene polymorphisms showed that there were significant correlations between rs901823 in gene LPR5 or rs2853561 in gene VDR and osteoporosis in patients with COPD.Further study is needed about the susceptibility and pathogenesis of LRP5 and VDR genes in osteoporosis in patients with COPD..