维生素D受体基因和雌激素受体基因多态性与老年人低骨量的关系

目的探讨维生素D受体基因(VDR)和雌激素受体基因(ESR1)多态性与老年男性、女性低骨量的关系。方法 378名老年男性[平均年龄(61.1±7.0)岁,其中260名健康男性、110例骨量减少和8例骨质疏松患者]和334名绝经后妇女[平均年龄(58.4±6.3)岁,其中148名健康女性、153例骨量减少和33例骨质疏松患者]共712人,均为居住在上海30年以上汉族人。用双能X线测量仪检测上述受试者左侧股骨颈骨密度(bone mineral density,BMD)。按照股骨颈BMD低于同性别正常峰值BMD的-1～-2.5和-2.5标准差为标准诊断骨量减少和骨质疏松,排除继发性低骨量。检测VDR基因FokⅠ、ApaⅠ、CDX 2位点ESR 1基因的PvuⅡ和XbaⅠ位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)。结果 378名老年男性中,FokⅠ的基因型频率为FF(28.0%)、Ff(50.0%)和ff(22.0%),ApaⅠ的基因型频率为AA(9.5%)、Aa(43.4%)和aa(47.1%);CDX 2的基因型频率为AA(22.2%)、AG(45.8%)和GG(32.0%);PvuⅡ的基因型频率为PP(14.1%)、Pp(46.0%)和pp(39.9%);XbaⅠ的基因型频率为XX(5.0%)、Xx(36.8%)和xx(58.2%)。334名老年女性中,FokⅠ的基因型频率为FF(25.7%)、Ff(55.1%)和ff(19.2%),ApaⅠ的基因型频率为AA(10.2%)、Aa(44.0%)和aa(45.8%);CDX 2的基因型频率为AA(22.8%)、AG(47.9%)和GG(29.3%);PvuⅡ的基因型频率为PP(9.9%)、Pp(45.2%)和pp(44.9%);XbaⅠ的基因型频率为XX(2.1%)、Xx(36.8%)和xx(61.1%)。等位基因频率分布均符合Hardy-Weinberg定律。老年男性和女性的骨质疏松组、骨量减少组和骨量正常组之间上述基因SNP频率分布未见差异(P均0.05)。结论 VDR的FokⅠ、ApaⅠ及CDX 2位点和ESR 1的PvuⅡ及XbaⅠ位点多态性可能不是纳入本研究汉族老年男性和女性低骨量的风险因子,尚需更大样本量的实验予以证实。     

维生素D受体基因多态性与骨质疏松

近年实验研究证实，维生素Ｄ受体基因多态性与骨密度密切相关，且可占其遗传因素７５％左右，正常高加索人群可通过ＶＤＲ基因多态性预测ＢＭＤ，其中ｂｂ基因型者比ＢＢ基因型者其ＢＭＤ值可高出１５％左右，日本人的ＶＤＲ基因多态性分布频率显著不同于高加索人，其中ＢＢ型仅占１％，但不同基因型之间仍有相似于高加索人的ＢＭＤ差异；学者们对美国人、法国人、朝鲜人的观察，未发现ＶＤＲ基因多态性与ＢＭＤ有明显相关性。关于Ｖ     

雌激素和雌激素受体基因多态性与骨代谢异常的关系

骨质疏松是一种多基因调控的疾病 ,以骨量减少和骨的微观结构退化为特征 ,雌激素和雌激素受体基因多态性是其重要影响因素之一。雌激素与受体结合后 ,调节成骨细胞和破骨细胞的骨形成和骨吸收作用 ,而雌激素受体基因多态性则被认为与骨矿物质密度 (BMD)呈密切相关 ,尤其对绝经前妇女和男性的BMD起到了预测因子的作用     

基因多态性与骨密度的相关性

骨密度受遗传因素影响,骨密度测定是诊断骨质疏松的主要依据.维生素D受体、Ⅰ型胶原、雌激素受体、降钙素受体参与骨形成和骨代谢,其基因多态性决定骨密度.研究发现Wnt蛋白、人类白细胞抗原等基因多态性也与骨密度有关.本文就基因多态性与骨密度的相关性进行论述.     

护骨素基因多态性与老年男性骨质疏松症的关系

目的探讨护骨素（OPG）基因启动子区T950C单核苷酸多态性与老年男性骨质疏松症发生的关系。方法选择98例老年男性骨质疏松症患者和101例正常老年男性,利用聚合酶链反应—限制性片段长度多态性分析技术检测OPG T950C多态位点的基因型,分析比较两组之间OPG T950C位点基因型频率的差异。结果OPGT950C基因型频率分布符合Hardy-Weinberg平衡,OPG T950C位点CC基因型频率在老年男性骨质疏松症患者和正常老年男性之间具有统计学差异（P〈0.01）。结论OPG基因启动子区T950C位点多态性与老年男性骨质疏松症的发生有关,OPG C950C基因型可能是老年男性发生骨质疏松的遗传易感性指标。     

老年男性骨质疏松与M-纤维凝胶蛋白基因多态性的关系

目的探讨M-纤维凝胶蛋白基因（M—ficolin）的FCN1基因启动子1981碱基G〉A突变rs2989727多态性与老年男性骨质疏松症的关系。方法选择老年男性骨质疏松症患者108例,老年男性非骨质疏松症者（对照组）90例,检测骨密度和钙、磷、碱性磷酸酶等指标与M—ficolin的FCN1基因启动子1981碱基G〉A突变rs2989727多态性。结果老年男性骨质疏松症组与对照组M—ficolin的FCN1基因启动子1981碱基G〉A突变rs2989727多态性等位基因分布频率无统计学意义。结论FCN1基因M-ficolin的FCN1基因启动子1981碱基G〉A突变rs2989727多态性与老年男性骨质疏松发病可能无关。     

维生素D受体基因多态性与骨质疏松症的研究进展

骨质疏松症是遗传和环境因素共同参与的多因子复杂疾病.维生素D受体基因被认为是调控骨量的候选基因之一,但维生素D受体基因多态性与骨质疏松症(骨密度和骨质疏松性骨折两个表型)的关系在不同种族人群的研究仍存在争议,本文就维生素D受体基因多态性与骨质疏松症的关系予以综述.     

过氧化物酶体增殖物激活受体γ基因多态性与老年男性骨质疏松的相关性

目的 探讨过氧化物酶体增殖物激活受体γ(PPARγ)基因第6外显子C161→T单核苷酸多态性与老年男性骨质疏松的相关性.方法 采用聚合酶链反应限制性片段长度多态性分析法检测老年男性骨质疏松组、老年男性非骨质疏松组(对照组)的基因频率分布;采用双能X线吸收测定法检测老年男性骨质疏松组及对照组腰椎和股骨上端(大转子、股骨颈)的骨密度;酶联免疫法(ELISA)检测血清骨钙素.结果 PPARγ基因第6外显子C161→T的多态性,有CC、CT和TT 3种基因型,老年男性骨质疏松组携带T等位基因的频率高于对照组,CT+TT分别为40.4%和25.7%(P＜0.05);与对照组比较,老年男性骨质疏松组骨钙素水平、骨密度较低;与CC基因型比较,携带T等位基因型的骨密度更低.结论 PPAR7基因多态性与老年男性骨质疏松有关,T等位基因是老年男性骨质疏松的易感因素.PPARγ可能是骨质疏松的一个候选基因.     

WNK4基因多态性与新疆哈萨克族原发性高血压的关系

目的 探讨新疆哈萨克族WNK 4(with no K=lysine kinase)基因内含子10(intron10)多态性与原发性高血压间的关系,了解该基因多态性在哈萨克族人群中的分布情况.方法 采用直接测序法测定WNK 4基因intron10序列,确定单核苷酸多态性位点及类型,应用多聚酶链反应、限制性片段长度多态性技术(PCR-RFLP)对该位点进行基因分型,其中原发性高血压患者191例(高血压组)、健康对照组173例.结果 在WNK 4基因intron10发现一多态性位点(17号染色体上碱基1156666,G→A);PCR-RFLP分型,GG、GA、AA各基因型在哈萨克族高血压组和健康对照组的频率分别为88.0%、11.0%、1.0%和91.9%、8.1%、0%,差异无统计学意义(均为P＞0.05);A等位基因频率分别为6.5%和4.0%,差异无统计学意义(P＞0.05).结论 WNK 4基因intronl0多态性可能不是新疆哈萨克族原发性高血压的遗传易感指标.     

雌激素和雌激素受体基因多态性与骨代谢异常的关系

骨质疏松是一种基因调控的疾病，以骨量减少和骨的微观结构退化为特征，雌激素和雌激素受体基因多态性是其重要影响因素之一。雌激素与受体结合后，调节成骨细胞破骨细胞的骨形成和骨吸收作用，而雌激素受体基因多态性则被认为与骨矿物质密度（ＢＭＤ）呈密切相关，尤其对绝经前妇女和男性的ＢＭＤ起到了预测因子的作用。     

Association of BsmI vitamin-D receptor gene polymorphism with combined bone mass in spine and proximal femur in Icelandic women

OBJECTIVE: To evaluate whether there is an association between BsmI-vitamin-D receptor (VDR) gene polymorphism and combined bone mass in the spine and proximal femur in a group of adult Icelandic women with high and low bone mineral density (BMD). DESIGN: Comparison of distribution of VDR genotypes (BB, Bb and bb) and allele frequency (B and b) in two groups of women: a group with 'strong bones' with high BMD in both the spine and proximal femur (> 1 standard deviation [SD]) above the age-matched mean (n = 35) and a group with 'weak bones' with BMD > 1.5 SD below the age-matched mean at both sites using dual energy X-ray absorptiometry. SETTING: Iceland, a population with a mean calcium intake > 1000 mg day-1. The calcium intake in the study group was however not evaluated. SUBJECTS: Eighty-three Icelandic women, aged 22-65, free of diseases affecting bone and not taking drugs affecting calcium or bone metabolism, recruited from women undergoing bone densitometry at the Reykjavik Hospital. MAIN OUTCOME MEASURES: Frequency of VDR genotypes and alleles in the two groups. RESULTS: The distribution of VDR genotypes was significantly different in the two groups (P < 0.01); the b allele frequency was 70% in the group with high BMD compared to 48.5% in the group with low BMD. CONCLUSIONS: In this selected group of adult Icelandic women the b allele in the vitamin-D receptor gene seems to be associated with high bone mass in the spine and proximal femur.     

不同骨量老年男性血清vaspin水平变化及意义

目的观察不同骨量老年男性血清内脏脂肪特异性丝氨酸酶抑制剂(vaspin)水平变化,并探讨其意义。方法选择在日照市人民医院健康查体的60~80岁的老年男性210例为研究对象,根据骨密度(BMD)将其分为正常组、骨量减少组、骨质疏松组。收集其基础资料(年龄、身高、体质量),测定血清学指标[血清Ca、血清P、血脂(TG、TC、LDL、HDL)、空腹葡萄糖(Glu)]及骨代谢五项,后者包括甲状腺旁腺素(PTH)、25羟维生素D[25(OH)D]、骨钙素(OC)、血清1型胶原C末端肽(CTX)、1型胶原N端前肽(P1NP);应用ELISA试剂盒检测血清vaspin水平;应用双能X线骨密度仪(DXA)检测股骨颈(FN)和腰椎(LS)两个部位的BMD;应用生物电阻抗法(BIA)测定人体成分组成,计算骨骼肌指数(SMI)。采用Spearman相关分析不同骨量老年男性血清vaspin水平与上述各指标的关系。将单因素分析中有统计学意义的因素纳入多因素logistic回归,分析其与老年男性骨质疏松症的关系。结果骨量减少组及骨质疏松组血清vaspin水平显著低于正常组,其中以骨质疏松组水平最低(P均<0.05)。在老年男性骨质疏松组,血清vaspin水平与HDL、P1NP、FNBMD及SMI呈正相关(r=0.676,P=0.007;r=0.548,P=0.016;r=0.683,P=0.003;r=0.510,P=0.025),与CTX呈负相关(r=-0.645,P=0.008)。在骨量减少组,血清vaspin水平与HDL、P1NP、FN BMD及SMI呈正相关(r=0.349,P=0.041;r=0.339,P=0.045;r=0.483,P=0.035;r=0.450,P=0.039),与CTX呈负相关(r=-0.441,P=0.040)。logistic回归分析结果表明,血清vaspin水平(OR=0.774,95%CI:0.655~0.856,P=0.002)是老年男性骨质疏松症的保护因素。结论骨量减少及骨质疏松老年男性血清vaspin水平降低,高水平血清vaspin可能是老年男性骨质疏松症的保护因素。     

Normative bone mineral density values in Filipino women

Objective: To obtain reference values of bone mineral density (BMD) for Filipino women in order to make a population‐specific diagnosis of osteoporosis. Method: Sudy design: Cross‐sectional. Setting: Osteoporosis Unit, Joint and Bone Center, Section of Rheumatology and Clinical Immunology, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines. Participants: 442 healthy Filipino women volunteers recruited from the outpatient department, Rheumatology and Clinical Immunology Clinic of the University of Santo Tomas Hospital and from within the University of Santo Tomas campus. Subjects with known underlying illness or conditions or intake of drugs that predispose to osteoporosis were excluded from the study. Intervention: Bone mineral density (BMD) measurements, expressed in grams per square centimenter of the lumbar spine, non‐dominant femur and non‐dominant forearm were done in 442 consecutive healthy Filipino women using the LUNAR DPX‐IQ machine. Results: Means and standard deviations of BMD measurements at each site were calculated using Kwikstat software Version 3.6, Release 7. Results were grouped in decades to serve as reference per decade. Conclusion: Bone mineral density measurements of these 442 healthy Filipino women may serve as an initial reference guide for the diagnosis of osteoporosis in Filipino women.     

Effects of androgens on bone in men and women

Although the beneficial effects of estrogen on bone have been proven in multiple well-designed clinical trials, with respect to testosterone and androgens, the data are less definitive. Testosterone appears to have a role in the development and maintenance of bone mass; however, the mechanism by which androgens exert their effects on bone is still not clearly understood. Despite the increasing use of testosterone supplementation in men and women for the prevention and treatment of osteoporosis, in sufficient evidence exists to support the widespread use of these agents for this indication at this time. The data supporting the beneficial effects of testosterone on bone mineral density are more convincing in hypogonadal men than in men with normal testosterone levels, or in women. The transdermal route of administration is often preferred for testosterone therapy because it avoids the first-pass metabolism associated with oral formulations and the pain experienced with intramuscular injections. Other androgens, including an abolic steroids and dihydroepiandrosterone, have also been used. In addition to monitoring for therapeutic response on initiation of androgen therapy, assessment for potential adverse events should be implemented. This should include assessment for adverse effects on the liver and alterations in the lipid profile in both men and women. Men should also be monitored for prostate growth, gynecomastia, priapism, decreased libido, and erythrocytosis, whereas women should be monitored for virilizing effects. Ongoing research into the pathophysiology and clinical effects of testosterone on bone will provide more insights regarding the utility of androgens in these populations.     

Association of single nucleotide polymorphisms in secreted frizzled-related protein 1 gene with bone mineral density in Japanese women

Aim:   Recent studies have demonstrated that the Wnt signaling pathway plays an important role in bone metabolism. The purpose of this study was to examine whether the gene of secreted frizzled-related protein 1 ( SFRP1 ), a Wnt antagonist, is involved in the etiology of osteoporosis using association study.
Methods:   Seven single nucleotide polymorphisms (SNP) in the SFRP1 gene were genotyped and analyzed for association with bone mineral density (BMD) in 931 Japanese women (63.5 ± 6.7 years old, mean ± standard deviation).
Results:   One SNP (rs16890444) located in intron and another (rs3242) located in the 3'-untranslated region of the sFRP1 gene were significantly associated with the lumbar spine BMD value, and BMD values for both the femoral neck and the total hip, respectively. Women with the T/T genotype of the former SNP had a lower BMD value of the lumbar spine (L2–L4) compared with those with C/C or C/T (BMD value adjusted for age, duration after menopause, and body mass index: 0.781 vs 0.830, P  = 0.037), while women with the T/T genotype of the latter SNP had higher BMD values of femoral neck and total hip compared with those with C/C or C/T (adjusted BMD value: femoral neck, 0.721 vs 0.633, P  = 0.025; total hip, 0.834 vs 0.737, P  = 0.027).
Conclusion:   These results suggest that the SFRP1 may be a candidate gene for a BMD determinant, but further studies need to consolidate the present findings.     

Depressive symptoms and rates of bone loss at the hip in older women

OBJECTIVES: To ascertain whether depressive symptoms are associated with increased rates of bone loss at the hip. DESIGN: Population-based prospective cohort study. SETTING: Four clinical centers in the United States. PARTICIPANTS: Four thousand one hundred seventy-seven community-dwelling women, aged 69 and older, enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Subjects were categorized as depressed if their GDS score was 6 or greater at the fourth examination. Bone mineral density (BMD) at the hip was measured using dual-energy x-ray absorptiometry at the fourth and sixth examinations (average 4.4 years between examinations). Use of antidepressant medications was assessed by interview and verified from medication containers at the fourth and sixth examinations of the Study of Osteoporotic Fractures. A computerized dictionary was used to categorize type of medication. RESULTS: In age-adjusted models, mean total hip BMD decreased 0.69%/year in 3,977 women with a GDS score of less than 6, compared with 0.96%/year in 200 women with a GDS score of 6 or greater (P<.01). Results were not substantially altered when adjusted for potential confounders and when users of antidepressants were excluded from the analysis. CONCLUSION: Depression, as defined by a GDS score of 6 or greater, was associated with an increased rate of bone loss at the hip in this cohort of older women. Clinicians should be aware of a possible increased rate of bone loss in older, depressed women.     

Association of a single nucleotide polymorphism in the secreted frizzled-related protein 4 (sFRP4) gene with bone mineral density

Background:   Wnt-β-catenin signaling pathway is involved in the regulation of bone mineral density (BMD). Secreted frizzled-related protein (sFRP) 4 that antagonize Wnt signals may modulate Wnt-β-catenin signaling pathway in the bone. Therefore, we analyzed expression of sFRP4 mRNA in primary osteoblasts and the association of a single nucleotide polymorphism (SNP) in the sFRP4 gene with BMD.
Methods:   Expression levels of sFRP4 mRNA were analyzed during the culture course of rat primary osteoblasts. Association of a SNP in the sFRP4 gene at Arg262 (CGC to CGT) with BMD was examined in 372 healthy post-menopausal Japanese women.
Results:   sFRP4 mRNA was detected and increased during the differentiation of rat primary osteoblasts. As an association study of the SNP in the sFRP4 gene, the subjects without the T allele (CC; n  = 129) had significantly higher lumbar BMD than the subjects bearing at least one T allele (TT + CT; n  = 243) (Z score; 0.054 versus −0.324; P  = 0.0188).
Conclusion:   sFRP4 mRNA was expressed and regulated in primary osteoblasts. A genetic variation at the sFRP4 gene locus is associated with BMD, suggesting an involvement of sFRP4 gene in the bone metabolism.