维生素D受体基因BsmI多态性与儿童佝偻病的关系研究

目的研究维生素D受体(VDR)基因BsmI多态性分布，以及与维生素D缺乏性佝偻病的关系,探讨其遗传易感性。方法对象为41例维生素D缺乏性佝偻病患儿和68例健康对照组儿童，均为山西籍汉族儿童，应用聚合酶链反应 限制性片段长度多态性分析(PCR RFLP)等技术测定VDR基因BsmI多态性,比较两组基因型和等位基因的分布频率，并用Hardy Weinberg遗传平衡检验方法进行基因分布遗传平衡吻合度检验。结果佝偻病患儿组Bb、bb基因型分布频率分别为14.6%和85.4%，健康对照组儿童Bb、bb基因型分布频率分别为19.1%、80.9%。病例组等位基因B、b分布频率分别为7.35%、92.7%，对照组等位基因B、b分布频率分别为9.6%、90.4%，佝偻病组和正常对照组VDR基因型Bb、bb分布频率和等位基因分布频率间没有显著性差异。BsmI多态性分布极不平衡，bb型最多占80.9%，b位点占90.4%，是优势基因。结论VDR基因BsmI酶切位点多态性与维生素D缺乏性佝偻病发病无明显相关性。     

汉族女性峰值骨密度和维生素D受体基因多态性及环境因素的相关性研究

目的　研究汉族女性峰值骨密度 (peakbonemineraldensity ,PBMD)与某些环境及遗传因素的关系。方法　选择健康的志愿者 1 5 9人 ,①通过饮食回顾法计算每日钙及蛋白入量 ;②通过 7d运动评估法计算运动强度 ;③使用DEXA骨密度仪 (HologicQDR 4 5 0 0 )测量志愿者腰椎和髋部骨密度 (BMD) ;④应用PCR -限制性片段长度多态性对维生素D受体 (VDR)基因进行多态性分析。结果　①腰椎BMD结果参照日本人标准 ,低骨量或骨质疏松共有 35人 (2 2 % ) ,正常骨量者为 1 2 4人 (78% )。两组间体重及体重指数 (BMI)间有显著差异 ;②腰椎及髋部股骨颈BMD与体重呈正相关 ,髋部其余位点BMD值和BMI呈正相关 ;③VDR基因BsmI酶切多态性组间BMD无显著性差异。结论　本研究显示 :体重及或BMI是汉族女性PBMD重要保护因素之一。汉族女性PBMD和当前营养状态、运动强度、VDRBsmI酶切位点基因多态性未见有相关性     

北京地区女性峰值骨密度与雌激素受体基因多态性的相关因素分析

目的 探讨影响北京女性峰值骨密度(peak hone mineral density，PBMD)和雌激素受体(estrogen receptor，ER)基因多态性的关系。方法 于2000年3月～2001年7月，选择健康志愿者159人，①使用DEXA(Holooc QDR4500)测量志愿者腰椎和髋部BMD；②从志愿者静脉全血(5～10ml)中提取DNA，应用PCR-限制性片段长度多态性法(restriction fragment length polymorphisms，PCR-RFLP)对ER进行多态性分析；③分析PBMD与身高、体重、体重指数(BMI)及ER基因多态性的相关关系。结果 ①腰椎BMD和身高、体重及BMI呈正相关，髋部股骨颈(Neck)位点BMD值和体重呈正相关，而髋部其余位点BMD值和BMI呈正相关．且Ward三角与ER PvuⅡ酶切位点有相关性；②ER基因PvuⅡ酶切结果显示在髋部Ward三角，PP基因型组的BMD明显低于Pp及pp基因型组，差异有显著性；③ER PvuⅡ和XbaI酶切位点的联合分析，PPxx基因型组BMD值在各位点均较高，PPXx基因型组BMD值在各位点均最低，在髋部股骨颈、粗隆间差异有显著性。在Ward三角位点，Ppxx基因型BMD值最高，与PPXx及PPXX基因型组有显著性差异，PPxx基因型组BMD值也较高。结论 ①体重及或BMI是女性PBMD重要保护因素之一；②ER基因多态性影响中国汉族女性峰值BMD结果。     

1477例孕妇VDR基因FokI位点多态性与25-羟维生素D的相关性研究

目的:研究孕妇VDR基因FokI位点多态性与25-羟维生素D的相关性。方法:随机抽取2016年6月至2018年12月于温州市中心医院产检的1477例孕妇作为研究对象。PCR-焦磷酸测序法检测VDR基因FokI位点多态性,ELISA法检测血清25-羟维生素D水平,分析两者的相关性。结果:1477例孕妇中,VDR基因Fok I位点TT、TC、CC基因型分别有353例(23.90%)、702例(47.53%)和422例(28.57%)。TT、TC、CC基因型组的血清25-羟维生素D平均浓度分别为(30.93±9.42)nmol/L、(41.32±8.43)nmol/L和(51.34±9.82)nmol/L,3组比较差异有统计学意义(P0.05)。结论:孕妇VDR基因多态性Fok I位点与血清25-羟维生素D水平有相关性,TT基因型的血清25-羟维生素D浓度最低,CT型次之。建议孕妇行VDR基因FoK I多态性及血清25(OH)维生素D水平检测,个体化补充维生素D,预防新生儿先天性佝偻病的发生。     

北京地区青年峰值骨密度与遗传因素的相关性分析

目的　探讨北京地区女性峰值骨密度 (PBMD)与遗传因素的关系。方法　于 2 0 0 0年 3月至 2 0 0 1年 7月 ,选择居住在北京、汉族女性、年龄 2 5～ 37岁的健康志愿者 1 59名 ,(1 )使用双能X线吸收仪 (DXEA)测量腰椎和髋部BMD ;(2 )抽取静脉血 5～ 1 0ml,提取DNA ,应用多聚酶链反应 限制性片段长度多态性法 (PCR RFLP)对维生素D受体 (VDR)和雌激素受体 (ER)进行多态性分析 ;(3)分析PBMD与身高、体重、体重指数 (BMI)、VDR及ER基因多态性的相关关系。结果　 (1 )腰椎BMD和身高、体重及BMI呈正相关 ,髋部股骨颈BMD和体重呈正相关 ,而髋部其余部位BMD和BMI呈正相关 ;(2 )VDR基因经BsmⅠ酶切 ,bb基因型者的腰椎、髋部 (除Ward三角 )BMD高于Bb基因型者 ,但两者间差异无显著性 (P >0 0 5) ;(3)ER基因经PvuⅡ酶切 ,髋部Ward三角PP基因型者的BMD[(0 73±0 1 4 )g/cm2 ]明显低于Pp及pp基因型者 [(0 78± 0 1 6)与 (0 79± 0 1 6)g/cm2 ] (P <0 0 5) ;(4)VDR和ER基因联合分析 ,腰椎bbPP基因型者BMD[(1 0 5± 0 0 9)g/cm2 ]最高 ,BbPP基因型者BMD[(0 94±0 0 8)g/cm2 ]最低 ,两者差异有显著性 (P <0 0 5) ;髋部各部位BbPP基因型者BMD均最低 ,但校正体重后 ,各基因型者之间差异无显著性 (P >0 0 5)。结     

维生素D受体基因多态性与佝偻病关系的研究

探讨维生素D受体基因多态性与维生素D缺乏性佝偻病（佝偻病）遗传易感性的关系。方法 　应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP ）分析技术检测2003年10月至2004年10月159例佝偻病患儿和78名健康儿童（对照组）VDR基因BsmⅠ位点的多态性,比较两组之间VDR基因型和基因分布。结果　 佝偻病患儿和对照组儿童的VDR基因Bsm I位点基因型分布分别为：BB（0％）,Bb（15.7％）,bb（84.3％）和BB（0％）,Bb（11.5％）,bb（88.5％）,两组 间差异无统计学意义（P >0.05）;佝偻病患儿和对照组儿童的VDR基因Bsm I位点等位基因分布分别为：B（7.9％）,b（92.1％）和B（5.8％）,b（94.2％）, 两组间差异无统计学意义（P > 0.05）。结论　VDR基因BsmⅠ酶切位点的多态性与维生素D缺乏性佝偻病的遗传易感性相关关系尚须大样本进一步确定。     

维生素D受体基因多态性与中国汉族儿童结核病易感性的研究

目的　探讨维生素D受体（VDR）基因多态性与中国汉族儿童结核病易感性的关系。 方法　收集2005年1月至2008年3月北京儿童医院收治的125例汉族儿童 结核病患儿,以同期在北京儿童医院门诊行外科手术（如疝、牙齿矫正、鞘膜积液等）前查体的446例患儿作为对照,对照组无结核病史,X线胸片无异常,PPD皮 试硬结直径小于5 mm,按照年龄、性别以及居住地与病例组进行匹配,采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测VDR基因上的Fok I和Taq I位点多态性,采用SPSS 12.0软件对病例组和对照组的基因型和等位基因频率进行卡方检验。 结果　结核组和对照组Fok I位点的FF、Ff、ff基因型频率分别为 29.6%、51.2%、19.2%和27.6%、50.9%、21.5%;Taq I位点的TT、Tt、tt基因型频率分别为90.4%、9.6%、0和86.8%、13.0%、0.2%;结核组和对照组在基因型频率 和等位基因频率分布上差异均无统计学意义。将样本按性别进行分组比较后发现,不同性别中病例组和对照组儿童的基因型和等位基因频率之间的差异无统计学 意义。 结论　VDR基因上的Fok I和Taq I位点的多态性与中国汉族儿童结核病的易感性无明显相关性。     

纤溶酶原激活物抑制物 1基因启动子区4G/5G多态性与川崎病冠状动脉损伤的关系

目的探讨纤溶酶原激活物抑制物 1(PAI 1)基因启动子区4G/5G多态性与中国汉族儿童川崎病(KD)的关系。 方法对2001—2003在深圳市儿童医院就诊的KD患儿126例，用等位基因特异性聚合酶链反应(AS PCR)检测126例患儿和120名健康儿童PAI 1基因启动子区4G/5G多态性；用发色底物法检测各组PAI 1血浆活性。 结果(1)KDⅠ组(合并冠状动脉损伤)和KDⅡ组(无冠状动脉损伤)患儿PAI 1血浆活性均高于健康对照组，差异有显著性(P均<005)。KDⅠ组PAI 1血浆活性高于KDⅡ组，差异有显著性(t=978，P<005)。(2)KDⅠ组和KDⅡ组中4G/4G基因型PAI 1血浆活性明显高于4G/5G基因型和5G/5G基因型，差异有显著性(均P<005)。(3)KDⅠ组4G/4G基因型频率显著高于KDⅡ组(P<005)和健康对照组(P<005)。与非4G/4G纯合子基因型相比，4G/4G纯合子基因型对KD冠状动脉并发症的比值比(OR)为280(95%置信区间：125~629，P<005)。 结论PAI 1基因启动子区4G/5G多态性与KD冠状动脉损伤密切相关，PAI 1基因启动子区4G/4G基因型可作为KD冠状动脉损伤高危人群的基因标志。     

多巴胺转运体440bp等位基因与儿童孤独症的关系

目的探讨儿童孤独症(CA)与多巴胺转运体(DAT1)440bp等位基因的关系。 方法陕西省纺织医院等于2004年3~8月，采用PCR技术对来自西安市两所康复中心的汉族CA儿童与DAT1基因多态性进行遗传关联分析。 结果(1)DAT1基因多态性中共观察到5种等位基因(320bp，360bp，440bp，480bp，520bp)，6种基因型(480/480，480/320，520/480，480/360，480/440,440/440)。(2)使用相对危险度RR对CA与DAT1基因多态性的等位基因和基因型进行关联分析，显示480/440基因型和等位基因440与CA呈正关联，相对危险度分别为265和230，480/480基因型和等位基因480与CA呈负关联，相对危险度分别为064和077。但统计结果没有发现具有统计意义的差异。 结论中国汉族CA儿童与DAT1440bp等位基因无遗传关联。也许等位基因440bp与基因型480bp/440bp这两个因素是发病的风险因素,还有待今后的进一步研究。     

TBX1基因多态性与先天性心脏病的相关性

目的探讨TBX1基因多态性与先天性心脏病(先心病)的相关关系。 方法选择2004-10—2005-03在哈尔滨医科大学附属第二医院住院的先心病患儿99例，对照组96名(与先心病患儿年龄相近的健康儿童)。应用小剂量DNA提取技术及采用ABI Prism SNaPshot方法,检测了先心病患儿和对照组儿童的TBX1基因多态性。 结果经χ2检验，TBX1基因各基因型频率在对照组、先心病组之间均无显著性差异(P>005)；各等位基因频率在两组人群中差异均无显著性意义(P>005)。 结论未发现TBX1基因多态性与先天性心脏病之间存在相关关系。     

Vitamin D receptor polymorphism in the group of postmenopausal women with low bone mineral density

OBJECTIVES: Osteoporosis is a multifactoral disease with aetiology depending from the hormonal, environmental, and genetic factors. One of the suggested candidate gene involved in the pathogenesis is the polymorphic gene encoding for vitamin D receptor (VDR). VDR polymorphism was connected with bone mineral density (BMD) and correlated with onset of osteoporosis. The goal of our study was to determine the role of BsmI polymorphism of VDR gene in the group of postmenopausal women with low bone mineral density. MATERIALS AND METHODS: We have analysed the group of 34 postmenopausal women. The DNA analysis was performed using PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) assays. RESULTS: In our investigation we have observed statistically higher frequency of B allele (48.5% vs. 41.2%), the lower frequency of b allele (51.5% vs. 58.8%) and bb genotype (8.8% vs. 42.5%) in the investigated group of postmenopausal women with low BMD. CONCLUSIONS: Our observations could suggest the important role of B allele of the VDR gene in the pathogenesis of osteoporosis in the group of women with low mineral density and possible protective role of b allele in this disease.     

北京地区汉族绝经后妇女雌激素受体基因多态性与尺桡骨骨密度相关性研究

目的　研究雌激素受体（ER）基因多态性在北京地区汉族绝经后妇女中的分布及其与骨密度的相关性。方法　对绝经1～4年、年龄49～55岁未行激素替代治疗且无对骨密度有影响疾病的健康绝经后北京市区汉族妇女99例,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定ER基因的XbaⅠ和PvuⅡ酶切多态性,用双能X线吸收测量法检测桡骨骨密度（以骨密度T-score值表示）,方差法分析ER基因多态性与骨密度的关系。结果　ER基因PvuⅡ酶切多态性与尺桡骨松质骨（尺桡骨远端）、密质骨（尺桡骨近端）的骨密度无相关性(P>0.05),而ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度有相关性(P<0.05);XX基因型骨密度值最低密质骨为-1.55±0.37、松质骨为-2.54±0.38,xx基因型骨密度值最高密质骨为-0.95±0.24、松质骨为-1.74±0.16。结论　ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度间显著相关,不同个体的基因差异可能影响骨质疏松症的发生、发展。     

Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin D receptor FokI start codon polymorphism to bone mineral density and the occurence of osteoporosis. METHODS: We determined the vitamin D receptor FokI start codon polymorphism using polymerase chain reaction-based restriction analysis in 163 postmenopausal women in Taiwan. The vitamin D receptor gene polymorphism was detected by the restriction enzyme FokI, where the F allele indicated the absence of the cuttable site and the f allele its presence. We then related the genotypes to bone mineral density and the occurence of osteoporosis in these women. RESULTS: The allelic frequencies for 163 postmenopausal women in Taiwan were 59.2% for F and 40.8% for f in FokI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 42.3% FF, 33.7% Ff and 24% ff. The three genotypic groups differed significantly in bone mineral density at the lumbar spine (P = 0.029). Bone mineral density was highest in the Ff group and lowest in the ff group at the lumbar spine and the femoral neck. The FokI vitamin D receptor genotype showed a significant effect on the prevalence of osteoporosis in the subjects at the lumbar spine. That is, women with genotype ff had a 2.8 times greater risk for osteoporosis (P < 0.05), and those with genotype FF had a 0.8 times greater risk than women with genotype Ff. CONCLUSION: Our findings indicate that the vitamin D receptor FokI start codon polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine.     

The role of vitamin D receptor genes (FOKI and BSMI) polymorphism in osteoporosis

ObjectiveTo evaluate the pattern of vitamin D receptor (VDR) genes polymorphism in postmenopausal Egyptian females for possible genetic role.DesignProspective cross sectional study.Participants and methodsEgyptian postmenopausal women with and without osteoporosis were diagnosed by bone mineral density measurement then were subjected to identification of VDR genes (FOKI and BSMI) polymorphism by PCR technique followed by RFLP analysis.ResultsThe frequencies of BB, Bb and bb genotypes (BSMI polymorphism) in patients were 54%, 30% and 16%, respectively. While, in controls their frequency was 5%, 10% and 85%, respectively. The BB genotype was higher in patients than in controls (P=0.001) while the bb genotype was significantly higher in controls than in patients. Regarding the FOKI polymorphism the frequencies of FF, Ff and ff genotypes among patients were 68%, 18% and 14%, respectively while their frequency in controls were 100%, 0% and 0%, respectively. Postmenopausal females carrying either B+ve or f+ve genotype were more risky to develop osteoporosis (OR of 29.75, 1.59, respectively).ConclusionThe BB genotype was higher in patients than controls and the bb genotype is a protective genotype. The FF genotype was predominant among post menopausal females and ff genotype was associated with osteoporosis. Currently, however, the mechanisms by which VDR alleles regulate BMD remain poorly understood.     

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.     

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024?+?283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto's thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ(2) was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.