Association Of Purinergic P2Y1R And P2Y2R Polymorphisms And Environmental Factors With The Susceptibility To Primary Osteoporosis

Background and Objective: Primary osteoporosis(OP)has become one of the global public health problems which is characterized by high incidence,wide affected population,complicated pathogenic factors and severe consequences.The incidence of OP lists at the seventh position of common diseases in the world.Postmenopausal women are high-risk population of OP.The main harm of OP is brittle fracture,giving rise to bone pain and even disability and death.It can also result in increasing social and family economic burden,and affect human health and quality of life.P2Y1receptor(P2Y1R)and P2Y2 receptor(P2Y1R),expressed in osteoblasts as well as osteoclasts,are G protein-coupled receptors with a wide range of biological effects and play important roles in the process of bone reconstruction.Genetic factors and environmental factors are important factors in determining the pathogenesis of OP.Several studies have indicated the association between P2 Y receptors and the risk to OP in Caucasians.However,there are racial differences in single nucleotide polymorphisms(SNPs)and gene frequency distribution.Therefore,it is necessary to study the association of P2Y1 R and P2Y2 R polymorphisms with OP susceptibility in Chinese population.A case-control study was thus conducted to investigate the association of purinergic P2Y1 R and P2Y2 R polymorphisms and envirnmental factors with the susceptibility to OP,with an attempt to screen susceptibility genes and the risk environmental factors and find the potential susceptibility SNPs underlie OP.The results of this study may provide important information to prevent or delay the occurrence of OP.Methods:1.Epidemiological survey methods were conducted,dividing subjects into control group and OP group,randomly collecting blood samples of 274 postmenopausal women with OP and 195 controls,and extracting blood genomic DNA.Allele specific-PCR method was applied to identify the rs701265 and rs1371097 polymorphisms of P2Y1 R gene,as well as rs4944831,rs1783596,rs10898909,rs4382936 and rs12366239 polymorphisms of P2Y2 R gene.2.Unconditional logistic regression model was used to assess the effect of the P2Y1 R and P2Y2 R polymorphisms as well as the environmental factors on the OP susceptibility.3.Interactions of genes and environmental factors with OP susceptibility were analyzed by generalized multivariate dimensionality reduction(GMDR)method.Logistic regression model was used to assess the effect of the optimal model of gene and environmental factor interaction on the susceptibility to primary OP.Results:1.Low body mass index is a risk factor of OP occurrence(OR = 2.244,95% CI= 1.098-5.442,p = 0.029).Regular intake of milk is a protective factor from OP occurrence(OR = 0.157,95% CI = 0.070-0.350,p = 0.000)and physical activity is a protective factor from OP occurrence(OR = 0.262,95% CI = 0.133-0.518,p =0.000).2.P2Y2 R gene rs10898909G> A is associated with the susceptibility to OP and allele A is the risk allele of primary OP(OR = 1.358,95% CI = 1.041-1.772,p =0.024).3.P2Y1 R rs701265,P2Y2 R rs10898909 and physical activity have an interactive effect on the prevalence of OP in Chinese postmenopausal women.High level of physical activity,P2Y1 R rs701265-G allele and P2Y2 R rs10898909-G allele are the protective factors from OP(OR = 0.196,95% CI = 0.070-0.551,p = 0.002).Conclusion:1.Low body mass index is a risk factor of OP occurrence,but regular intake of milk and high level of physical activity are protective factors of OP occurrence.2.The P2Y2 R rs10898909G> A is associated with the risk to OP.P2Y2 R Rs10898909-A is the risk allele of primary OP.3.P2Y1 R rs701265,P2Y2 R rs10898909 and physical activity have an interactive effect on the prevalence of OP in Chinese postmenopausal women.High level of physical activity,P2Y1 R rs701265-G and P2Y2 R rs10898909-G are the protective factor from OP.