Association Between Estrogen Receptor Alpha Gene(ER?) Polymorphism And Osteoporosis In Postmenopausal Women In Henan Province

BackgroundPostmenopausal osteoporosis(PO)was one of the skeletal disorders in postmenopausal older women characterized by low bone mineral density(BMD),with consequent in pathological fractures,endangering the living quality of women.Osteoporosis was a multifactorial disease,and many factors,such as diet,drugs,physical activity,malnutrition,endocrine status etc,played an important role in osteoporosis.Estrogen receptor alpha gene(ER?)polymorphisms had been the most studied in the genetic regulation of osteoporosis in various populations.The relationship between rs9340799(XbaI),rs2234693(PvuII)polymorphisms of ER? gene and the BMD had been studied extensively in different races.However,the association has not been defined so far.To our knowledge this was the first study to report an association between rs3798577 polymorphisms and BMD in postmenopausal women.Through this study,we hope to provide a new clue for the early diagnosis and prevention of postmenopausal osteoporosis.Objective1 To investigate the relationship between the clinical data and the clinical risk factors for osteoporosis in postmenopausal women in Henan Province.2 To investigate the relationship between estrogen receptor alpha gene(ER?)rs9340799,rs2234693,rs3798577 polymorphisms and osteoporosis in postmenopausal women in Henan Province.Materials and methods1 Subjects.Between February 2014 and October 2015,a total of 142 postmenopausal female patients with a clinical diagnosis of osteoporosis and 151 age matched female inpatients without osteoporosis(excluding autoimmune diseases and using drugs interfering with bone metabolism;menopause years?10 years)were randomly recruited in Henan Provincial People's Hospital.2 BMD measurementBMD was measured at the lumbar spine(L2~L4)and left femoral neck by dual energy X-ray absorptiometry(Hologic,Inc.,Bedford,USA).The T-scores and Z-scores that indicate the quality of bone mass were calculated automatically.3 Clinical data collectionThe clinical data,such as age,menopause duration,height,weight,BMI index and so on,were collected from the hospitalized medical records,and Serum calcium(Ca),fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),high density lipoprotein-cholesterol(HDL-C)and low density lipoprotein-cholesterol(LDL-C)were collected from the clinical examination report system.4 Determination of ER? genotypesAbout 3-ml peripheral blood samples were collected in an EDTA anticoagulant tube from all the subjects.Genomic DNA was extracted from peripheral blood of each woman.ER? gene polymorphisms were analyzed by Polymerase chain reaction-ligase detection reaction(PCR-LDR).Results1 BMD values in postmenopausal women with osteoporosis and the control groupLumbar spine(L2~L4)BMD were 0.808±0.107(g/cm2)and 1.173±0.164(g/cm2)in postmenopausal women of the osteoporosis(n=142)and the control group(n=151)respectively.There was a highly statistically significant(P <0.001).2 Association of clinical data and the detection of BMD values with osteoporosisBMI(kg/m2),total cholesterol(mmol/L),fasting blood glucose(mmol/L)and diabetes were significantly different between the osteoporosis and the control group(P <0.05).No significant difference were found in other clinical indicators(P > 0.05).3 Genotype and allele distribution of the ER? gene polymorphisms between the osteoporosis and the control groupOur results showed significant differences between the osteoporosis and the control group regarding the CC,CT and TT genotypes of the rs2234693 polymorphisms(7.7%,37.3%,54.9% VS.19.8%,41.1%,39.1%;P <0.05).When compared to the control,rs2234693 CT and TT genotypes were associated with increasing the risk of osteoporosis in postmenopausal women(OR=2.331,P <0.05 and OR=3.606,P <0.05,respectively).Rs2234693 T allele carriers had higher osteoporotic risk than the subject with the C allele carriers in postmenopausal female(OR=1.889,P <0.05).We found the CT and TT genotypes carriers had a lower BMD in lumbar vertebrae(L2~L4)and femoral neck compared to the CC carriers(P <0.05)in postmenopausal women.There were significant differences between the osteoporotsis and the control group regarding the CC,CT and TT genotypes of the rs3798577 polymorphism(35.9%,43.0%,21.1% VS.45.1%,43.0%,11.9%;P <0.05).The frequency of TT genotype was significantly lower in the control than in the osteoporosis group.Rs3798577 TT genotype was also associated with increasing the risk of osteoporosis in postmenopausal women compared to CC genotype(OR=2.222,P <0.05).And rs3798577 T allele carriers had higher osteoporotic risk than the subject with the C allele carriers in postmenopausal female(OR=1.477,P <0.05).But there was no statistically significant decrease of the mean values of BMD in lumbar vertebrae(L2~L4)and femoral neck between rs3798577 genotypes(P > 0.05).No significant differences were found between rs9340799 polymorphisms and osteoporosis in postmenopausal women(P > 0.05).4 Association of ER? gene polymorphism haplotype with osteoporosisRs9340799,rs2234693 and rs3798577 polymorphisms of ER? gene showed strong linkage disequilibrium(LD),and the D'values were 0.861,0.797 and 0.775,respectively.H3-ATT haplotype carrier was associated with increasing the risk of osteoporosis in postmenopausal women(P <0.05),but H6-ACC haplotype carrier was associated with reducing the risk of osteoporosis in postmenopausal women(P <0.05).There was no significant difference in the frequency of other haplotypes between the osteoporosis and the control group(P > 0.05).5 Logistic regression analysis of the risk factors for osteoporosis in postmenopausal womenMultifactor logistic regression analysis showed that rs2234693 T allele carriers(OR=2.831,P <0.05),diabetes(OR=1.843,P <0.05)and total cholesterol(TC)?5.2 mmol/L(OR=1.681,P <0.05)were the risk factors for osteoporosis in postmenopausal women.Conclusions1 Total cholesterol(TC)?5.2 mmol/L and diabetic complication were the risk factors for osteoporosis in postmenopausal women of Henan Province.2 ER? gene rs2234693 polymorphisms might contribute to the susceptibility of osteoporosis in postmenopausal women,and the T allele carriers had higher osteoporotic risk than the subject with the C allele.Carrying rs9340799-rs2234693-rs3798577-ATT haplotype might increase the risk of osteoporosis in postmenopausal women in Henan Province.