The Association Study Of ABCB1 Polymorphisms And Glucocor Ticoid-induced Osteoporosis In Yunnan Han Population

Objective:To investigate the relationship among glucocorticoid induced osteoporosis and ABCB1 gene polymorphisms and clinical indicators of patients who are receiving glucocorticoid treatment. To explore the risk factors and predictors of glucocorticoid-induced osteoporosis.Methods:Our study included 77 patients receiving glucocorticoid treatment as GC group and 116 healthy individuals as control. According to Z score of bone mineral density, GC group was divided into normal subgroup and osteoporosis subgroup.The Bone mineral density of lumbar vertebra were detected by dual-energy X-ray absorptiometry (DXA).The clinical data was collected including gender, age, body mass index (BMI), the duration of glucocorticoid treatment and other clinical data.We used polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method to analyze the ABCB1 C3435T, C1236T, G2677T/A gene polymorphisms. The correlation between the above factors and glucocorticoid-induced osteoporosis was analyzed.Results:(1) The proportion of osteoporosis patients was 32.47% in the GC group,the proportion of osteoporosis patients was 11.21% in the control group,and the difference was statistically significant(P< 0.01);The mean value of LI-L4 BMD in the GC group was 1.03+0.15, which is statistically significantly lower than that in the control group(1.13±0.14),(P< 0.01);(2)In the GC group, the patients of osteoporosis subgroup had a longer time of taking GC and the primary disease progression than bone mass normal subgroups, the difference was statistically significant (P< 0.01).(3)There was no statistically significant difference of the frequency distribution of genotypes and alleles of ABCB1 gene C1236T, G2677T/A, C3435T between the normal group and the osteoporosis group and the common haplotypes of ABCB1 C1236T-G2677T/A-C3435T was TTT,TGC,CGC and CAC, meanwhile the frequencies distribution of these haplotypes were not statistically significant between the NOP subgroup and the OP subgroup.(4)There was no statistically difference of BMD the Z value between genotypes and alleles of ABCB1 C1236T, G2677T/A genes.(5)A linkage disequilibrium phenomenon was found among ABCB1 C1236T, G2677T/A, C3435T genes; There was a high level of linkage disequilibrium between G2677T/A and C3435T(D’= 0.81, r2= 0.48);there was a low level of linkage disequilibrium between C1236T and C3435T(D’=0.72, r2 = 0.19), also a low level of linkage disequilibrium was found between C1236T and G2677T/A (D= 0.64, r2= 0.16).According to the result of C1236T-G2677T/A-C3435T haplotypes, the TTT, TGC, CGC and CAC haplotypes is relatively common. (6)The frequencies of three SNPs genotypes and alleles had no differences among PNS group and control group.Also, no differences was found between RA group and control group.Conclusion:(1) The risk of osteoporosis is higher in the patients taking oral GC than in control people, which is associated with duration GC for treatment and might be associated with the progression of the primary disease. (2)ABCB1 C3435T and G2677T/A, C1236T gene polymorphisms do not relate with the osteoporosis induced by GC. There is no significant correlation between the common haplotypes TTI、 TGC、CGC、CAC and osteoporosis caused by GC. (3) The ABCB1 C3435T, C1236T, G2677T/A genotype polymorphism is not associated with NS susceptibility and RA susceptibility.