大豆异黄酮和钙对绝经妇女骨代谢的影响及与ER基因Px单倍型的关系

目的探讨补充大豆异黄酮和钙对绝经妇女骨代谢的影响及与ER基因Px单倍型的关系。方法应用多聚酶链反应-限制性片断长度多态性(PCR-RFLP)检测691名汉族45～65岁绝经妇女的ER-α的PvuII和XbaI酶切位点多态性,从497名PvuII-XbaI单倍体确定者中随机抽取93人测定BMD,将T<-1.5者纳为干预对象(共60人)进行为期一年的随机对照干预实验。将干预对象随机分为两组:补钙+VD组和补钙+VD+大豆异黄酮组。给予的剂量分别为:钙440mg/d;VD100IU/d;大豆异黄酮100mg/d,干预期为12mon。测定基线和终期的各项骨代谢生化指标。结果干预12个月后,补钙组和补钙+大豆异黄酮组,机体的雌激素水平均未见显著性的改变,而25-OH-D均水平升高(P=0.09),但两组间的变化率无显著性的差异;血清钙磷及反映骨形成的指标未见显著性改变。补钙组的抗酒石酸酸性磷酸酶-5b(Tracp-5b)较基线升高[变化率:23.4%(-22.9%～49.1%)],而补钙+大豆异黄酮组则较基线降低[变化率:-4.2%(-26.0%～17.6%)],两组的变化率有显著性差异(P<0.05),尿吡啶交联物(Pyd)和I型胶原N末端肽(NTx)则未见显著性改变。补钙组,non-Px基因型较Px基因型更容易出现Pyd升高,骨特异性碱性磷酸酶(BAP)降低。钙+大豆异黄酮的干预效果在两种基因型间没有差异.结论补充大豆异黄酮并不影响体内的雌激素水平。反应骨吸收的生化指标Tracp-5b对大豆异黄酮的作用较敏感。单纯补钙后骨代谢生化指标的改变受Px单倍体基因型的影响。

RELATIONSHIP BETWEEN ESTROGEN RECEPTOR GENE Px HAPLOTYPE AND THE EFFECT OF CALCIUM AND SOY ISOFLAVONE SUPPLEMENTATION ON BONE METABOLISM IN CHINESE POSTMENOPAUSAL WOMEN

Objective To investigate the relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone metabolism in Chinese postmen- opausal women. Method Six hundred and ninety one Chinese postmenopausal women aged between 45 and 65 years were enrolled in randomly control test for 12 months. The PvuII and XbaI polymorphisms of ER-αgene were detected using restriction fragment length polymorphisms (RFLP). In 497 carriers of definitive PvuII-XbaI haplotype , ninety three subjects were chosen randomly. Bone mineral density (BMD) were measured by dual energy X-ray absorptiometry (DXEA). Sixty subjects with T<-1.5 were randomlyassigned intervention groups and received either 100 mg soy isoflavone and 440 mg Ca and 100 IU VD supplement per day or 440mg Ca and 100 IU VD supplement per day. Bone relevant biochemical indicators were measured at baseline and after 12 months. Results After 12 months, neither of the supplements had any effect on estradiol (E2), serum Ca, serum P and bone formation biomarkers, but 25-OH-D was mildly increased (P=0.09). Serum Tracp-5b was reduced in Ca + isoflavone group [percent change:-4.2% (-26.0%～17.6%)] ,but increased in Ca group [percent change:23.4% (-22.9%～49.1%)]. The change of serum Tracp-5b was significantly different between the two group (P<0.05). In Ca group, the non-Px genotype was prone to higher urine pyridine (Pyd) and lower BAP than was Px genotype. ER gene Px haplotype had no effect on the changes of the bone biochemical indicators after soy isoflavone supplementation. Conclusion Soy isoflavone supplementation had no effect on serum estrogen level. Serum Tracp-5b seemed to be a sensitive indicator to assess the effect of soy isoflavone on bone metabolism. ER gene Px haplotype influenced the effect of Ca treatment on bone biochemical indicators.