Association Of Insulin-like Growth Factor Receptors Gene Polymorphisms With Postmenopausal Osteoporosis

Objectives: Through the research of distributions of insulin-like growth factor 1 receptor(IGF-IR rs2229765)and insulin-like growth factor 2 receptor(IGF-IIR rs629849)gene polymorphism in patients with postmenopausal osteoporosis and healthy postmenopausal women in Gansu province,we investigate the association between these two gene polymorphisms and osteoporosis in postmenopausal women.At the same time,through the study of the differences of serum insulin like growth factor 1 IGF-I)and insulin-like growth factor 2(IGF-II)level in postmenopausal osteoporosis patients and healthy postmenopausal women,we explore the relationship between postmenopausal osteoporosis and insulin like growth factor and the association of IGF-IR rs2229765 and IGF-IIR rs629849 polymorphism with serum insulin like growth factor.We aim to explore the pathogenesis of osteoporosis from molecular and gene level,which lays the theoretical foundation for the study of genetic mechanism of Gansu area China in postmenopausal women with osteoporosis.Methods: We totally enrolled 218 patients with diagnosis of postmenopausal osteoporosis(aged 45~73)and 270 age-matched healthy controls with normal BMD(aged45~73)in this case-control study.The BMD of lumbar spine and femoral neck was assessed using the by dual-energy X-ray absorptiometry.Blood samples of all subjects were collected to analyse serum osteocalcin(OC),bone alkaline phosphatase(BALP),the ?-CrossLaps(?-CTX),calcium(Ca),phosphoru(P),25-(OH)D,IGF-I and IGF-II.IGF-IR rs2229765 and IGF-IIR rs629849 single nucleotide polymorphism were detected using restriction fragment length polymorphisms(RFLP)-polymerase chain reaction(PCR)in 218 patients with postmenopausal osteoporosis and 270 postmenopausal women with normal bone mineral density.Results: There were no significant differences in age,menopause duration,height,weight and BMI(P>0.05)between osteoporotic women and controls.Compared to controls,osteoporosis patients had statistically significant lower mean values of BMD(P<0.01)at lumbar spine and femoral neck and serum OC,BALP,?-CTX levels(P<0.01).But there was no statistical significance between two groups as regard serum Ca and P levels(P>0.05).Osteoporotic women had significant lower mean levels of serum 25-(OH)D(P=0.04),IGF-I(P=0.02)and IGF-II(P=0.02)than controls.Genotypic distributions of the IGF-IR and IGF-IIR gene polymorphism were consistent with the Hardy-Weinberg equilibrium in control subjects(P>0.05).The AA genotype(29% vs.17%,P =0.001)and A allele(51% vs.40%,P=0.000)distributions of the IGF-IR rs2229765 polymorphism were significantly higher in the patients than controls.There was no significant difference in the distribution of GA genotype(44% vs.46%,X2=1.828,P=0.176)of IGF-IR between osteoporotic women and controls compared with GG genotype.Conditional logistic regression revealed that compared with the GG genotype of IGF-IR,the AA genotype(OR=2.40,95% CI:1.46-3.95;P=0.001)and GA+AA genotype(OR=1.62,95%CI:1.10-2.39,P=0.015)were associated with osteoporosis without adjustment for confounding factors.After adjustment for age,menopause duration,BMI,serum 25-(OH)D?IGF-I? IGF-II,the AA genotype(OR=2.15,95%CI:1.29-3.58,P=0.003)and GA+AA genotype(OR=1.49,95%CI:1.00-2.23,P=0.048)of rs2229765 was still statistically associated with an increased risk of osteoporosis compared with GG genotype.Osteoporotic women with the AA genotype were found to have a significant lower mean values of femoral neck compared to women with GG and GA genotype(P<0.05).Serum IGF-I analysis shown that women with AA(P=0.007)and GA(P=0.016)genotype had a lower mean serum IGF-I level when compared with GG genotype.Heathy women with the AA genotype were also found to have a significant lower mean values of femoral neck compared to women with GG(P<0.01)and GA genotype(P<0.05).Concerning IGF-IIR gene rs629849 polymorphism,there was no significant difference in distributions of genotype(P>0.05)and allele(P>0.05)between osteoporotic women and controls.The association between rs629849 polymorphism of IGF-IIR gene and the risk of osteoporosis was not identified(P>0.05).And there was no correlation between IGF-IIR rs629849 polymorphism genotypes and bone mineral density,bone metabolism index,serum IGF-1 and IGF-II level in postmenopausal women.Conclusions: Our results indicated that the IGF-IIR rs629849 polymorphism is not associated with postmenopausal osteoporosis.The rs2229765 polymorphism in IGF-IR gene increased the risk of postmenopausal osteoporosis and may change serum IGF-I level in postmenopausal women.And the low level of surem IGF-1and IGF-II is associated with postmenopausal osteoporosis.