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。     

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。     

营养性疾病

关爱儿童试点对降低中国西部农村地区3岁以下儿童营养不良的效果分析；骨碱性磷酸酶检测在维生素D缺乏性佝偻病诊断与疗效评估中的价值；杭州市儿童晚发佝偻病发病维生素D受体基因多态性及治疗研究；铅暴露对难治性佝偻病患儿的骨代谢及免疫功能影响的研究     

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。     

不同纬度下维生素D受体基因多态性 与佝偻病易感性关联性Meta分析

目的    探讨4个常见维生素D受体（VDR）基因位点（ForkI、BsmI、ApaI、TaqI）单核苷酸多态性（SNPs）与佝偻病易感性关联性并探讨日照量对其的影响。方法    制定原始文献的纳入和排除标准及检索策略。检索1980年1月至2011年1月中国期刊全文数据库（CNKI）、中文科技期刊数据库（VIP）、数字化期刊全文数据库（万方）、中国生物医学文献数据库（CBM）及PubMed、CALIS、Science Direct 数据库中4个位点SNPs与佝偻病易感性关联性关系为研究内容的文献,提取数据。对研究间异质性进行检验并选用适当模型对总人群及高、低纬度两个亚组人群分别进行数据合并,得出合并比值比（OR）及95%置信区间（CI）。探讨研究间异质性来源,最后进行影响性分析及发表偏倚检验。结果    共纳入22篇文献。Meta分析结果显示,ForkI位点总人群及亚组人群显性、隐性、共显性遗传模型分析均提示病例f等位基因暴露比低于对照组,差异具有统计学意义。总人群3个遗传模型合并OR（95%CI）分别为0.40（0.25～0.65）、0.41（0.31～0.55）、0.50（0.38～0.67）;高纬度人群分别为0.48（0.25～0.93）、0.43（0.23～0.80）、0.55（0.39～0.78）;低纬度人群分别为0.38（0.21～0.69）、0.41（0.29～0.57）、0.48（0.34～0.68）。BsmI位点总人群显性、共显性模型及高纬度人群3个遗传模型分析均提示病例B等位基因暴露比高于对照组,差异有统计学意义（P＜0.05）。总人群显性、共显性模型合并OR（95%CI）分别为2.15（1.11～4.16）、1.85（1.09～3.16）;高纬度人群3个遗传模型合并OR（95%CI）分别为2.86（1.33～6.16）、3.93（1.11～13.89）、2.66（1.33～5.31）;低纬度人群差异无统计学意义。ApaI位点仅在总人群隐性模型分析中发现其多态性与佝偻病易感性关联有统计学意义。TaqI位点仅在总人群及高纬度人群隐性模型分析中发现其多态性与佝偻病易感性关联有统计学意义。影响性分析显示Meta分析结果稳定,可信度较高。结论    ForkI位点f等位基因可降低佝偻病易感性;BsmI位点B等位基因使日照贫乏地区人群更易患佝偻病;ApaI、TaqI位点SNPs可能与佝偻病易感性无关。ForkI、BsmI位点与佝偻病易感性关联可能受研究对象日照暴露量影响。     

维生素D受体基因多态性与0~6岁汉族儿童骨密度关系的研究

目的研究维生素D受体基因多态性与0~6岁汉族儿童骨密度(BMD)的关系，为临床儿童低BMD的早期预防提供理论依据。 方法上海新华医院上海市儿科医学研究所2002年7月至2004年3月收集排除影响骨代谢疾病的上海地区0~6岁汉族儿童204例，进行问卷调查、体格测量；用原子吸收分光光度计测血清锌；用放射免疫法测血清25(OH)D3；用超声BMD仪测定胫骨中段骨密度；用聚合酶链反应 限制性片段长度多态性方法，分析4个限制性酶切位点(ApaI、TaqI、BsmI、FokI)的多态分布。用多因素协变量方差分析维生素D受体(VDR)基因多态性与BMD的关系。 结果多因素协方差分析消除血清25(OH)D3水平、血清锌水平、户外体育活动等因素对BMD的影响后，发现VDR基因BsmI酶切位点等位基因型和FokI酶切位点等位基因型与BMD相关，Bb基因型的BMD百分位数明显低于bb基因型，分别为2200%和4314%，差异有显著性(F=504,P<005)；ff基因型骨密度低于Ff与FF基因型，分别为2697%、3795%、5352%，差异有极显著性(F=811,P<0001)。而在Apa I、Taq I酶切位点，不同等位基因型与BMD无关(F=108、127，P>005)。 结论VDR基因在BsmI、FokI酶切位点的多态性与0~6岁汉族儿童BMD相关。     

维生素D受体基因多态性与多囊卵巢综合征Meta分析

目的 探讨维生素D受体(vitamin D receptor,VDR)基因多态性与多囊卵巢综合征(polycystic ovary syndrome,PCOS)发生的关系。方法 采用Meta分析方法,计算机检索MEDLINE、PREMEDLINE、Cochrane Library、中国期刊全文数据库(CNKI)、中国学术期刊数据库(万方数据库)等,收集有关病例对照研究或队列研究,由两位研究者独立进行文献筛选、资料提取和方法学质量评价后,采用Rev Man 5.3和Stata14.0软件进行Meta分析。结果 共纳入12个研究。Meta分析结果显示,对于VDR Fok I rs10735810(CT)和VDR Tru9I rs757343(GA)多态性,PCOS组与对照组相比差异无统计学意义(P0.05)。对于VDR Apa I rs7975232(AC)多态性的研究发现,显性模型(AA+AC vs.CC)(OR 0.88;95%CI 0.74~1.05;P=0.008)和等位基因频率(A vs.C)(OR 0.84;95%CI 0.74~0.95;P=0.004)在PCOS组与对照组比较差异有统计学意义。对于VDR Bsm I rs1544410(AG)多态性的研究发现,等位基因频率(A vs.G)(OR 0.86;95%CI 0.74~0.99;P=0.04)在PCOS组与对照组比较差异有统计学意义。对于VDR Taq1 rs731236(TC)多态性的研究发现,显性模型(TT+TC vs.CC)(OR 0.78;95%CI0.62~0.99;P=0.04)在PCOS组与对照组比较差异有统计学意义。结论 VDR Fok I和VDR Tru9I多态性与PCOS发病无关,VDR Apa I,VDR Bsm I及VDR Taq1多态性与PCOS发病可能相关。     

儿童维生素D、钙营养与营养性维生素D缺乏性佝偻病判定与评价现状

        儿童维生素D缺乏性佝偻病（vitamin D deficiency,Rickets）是由于维生素D缺乏导致的可预防性疾病,与维生素D和钙营养密切相关。近年来,研究发现非肌肉骨骼系统的疾病,包括癌症、代谢综合征、感染和自身免疫性疾病与维生素D水平不足密切相关［1-3］。由于许多观察性研究证实维生素D不足在世界许多地区普遍存在,包括工业性国家［4-5］。因此,儿童维生素D、钙营养与营养性维生素D缺乏性佝偻病再次受到关注,国内外对儿童维生素D、钙营养与维生素D缺乏性佝偻病的判定和评价也有了新认识。     

维生素D骨骼外研究进展

维生素D（vitamin D）是大家熟知的脂溶性维生素,维生素D对人类健康特别是儿童健康具有重要意义。维生素D缺乏性佝偻病是由于缺乏维生素D引起体内钙磷代谢异常,钙盐不能正常沉着在骨骼生长部分,骨骼钙化不良而致骨骼病变,多见于婴幼儿,影响小儿生长发育,是我国儿科重点防治的四病之一。临床发现维生素D缺乏性佝偻病除导致骨骼病变外,同时也可影响神经、肌肉、造血及免疫等组织器官的功能,此引起了人们对维生素D生理作用及临床意义的极大兴趣,近年来对维生素D的研究取得了重大进展［     

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     

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.     

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.     

The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women

Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women.

Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m², to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women.

Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ² = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes.

Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.     

Association between vitamin D receptor gene haplotypes and bone mass in postmenopausal Korean women

OBJECTIVES: The objective of the study was to evaluate the effect of vitamin D receptor (VDR) gene haplotypes on bone mineral density (BMD). STUDY DESIGN: The VDR Bsm I, Apa I, Taq I, and poly(A) polymorphisms were analyzed in 417 postmenopausal Korean women. Serum 1,25(OH)(2) vitamin D(3), osteocalcin, bone alkaline phosphatase, and CrossLaps were measured by immunoradiometric assay and enzyme-linked immunosorbent assay. BMD at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. RESULTS: At all skeletal sites, genotypes not carrying the baTL haplotype allele (uppercase letters signifying the absence, lowercase letters the presence, of the restriction site, and L a repeat length of more than 17) had significantly lower BMD than baTL homozygotes. The former genotypes were more prevalent in women with low bone mass than in healthy women. No significant differences in vitamin D(3) or bone markers levels were noted among the baTL haplotype genotypes. CONCLUSION: The VDR baTL haplotype allele is related to bone mass in Korean women.     

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.     

Expression of vitamin D and vitamin D receptor in chorionic villous in missed abortion

Abstract

The contemporary world despite its enough developed medicine and generally highly enlightened population faces a great problem of vitamin, micro-element and nutrient deficiency turning to become the XXI century pandemic. Along with that significant growth of interest can be seen towards vitamin D importance for reproductive physiology. The fact is that vitamin D receptors (VDR) have been detected in women's ovarium tissue, fallopian tubes, decidua and placenta. Some recent years studies have proven that vitamin D may act as immune regulator during implantation. During early pregnancy the trophoblast release vitamin D, which produces anti-inflammatory reaction and also induce decidual tissue growth for successive pregnancy. It was a comparison between the expression of Vitamin D and VDR in chorionic villous in cases of normal pregnancy and missed abortion groups. 64 samples of chorionic villous were taken: 32 from missed abortion and 32 from the induced abortion group. Abortive material was taken from two groups of women residing in North-West region of Russia: missed abortion and pregnancy terminated at woman's wish (induced abortion); 6–12 weeks of gestation, singleton pregnancy. Immune histochemical examination showed homogenous distribution of vitamin D and VDR expression in syncytiotrophoblasts, cytotrophoblasts and chorion villus stroma.Vitamin D expression relative area was 10,3% which is statistically different from the induced abortion group – 15,4% (p<0,01). VDR expression analysis showed its homogenous distribution in chorionic villus structures in both groups. High VDR expression was detected in chorion villus stromal components. In missed abortion group, the morphometry results showed distinctly lower relative area of vitamin D expression against the comparison group (35,9?±?1,8; 56,1?±?2,4 p?<?0,01). Also in missed abortion group, positively significant correlation has been determined between the level of vitamin D in blood and VDR relative area expression (r?=?0,412). In missed abortion group, definite vitamin D and VDR expression decrease was detected compared to the induced abortion group. The results witness vitamin D importance for pregnancy progress.     

Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), rs10735810 (FokI): a case–control study of lower Silesian women

Abstract

Context: The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial.

Objective: The objective of this study was to investigate for the first time in women with “classic” PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology.

Design: Ninety-two women with “classic” PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed.

Results: Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with “classic” PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups.

Conclusions: For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous “classic” PCOS phenotype.     

Vitamin D receptor gene polymorphism and cardiovascular risk variables in elderly Polish subjects

The aim of this work was to evaluate whether the FokI and BsmI polymorphisms of the VDR gene are associated with anthropometric and biochemical features of cardiovascular disease (CVD) in a Caucasian population aged over 65, participants of the Polish PolSenior study. We performed the study on randomly selected subjects: 427 women and 454 men aged over 65. Measurements of anthropometric parameters were carried out and biochemical parameters were estimated using commercial kits. VDR polymorphisms (rs10735810, rs1544410) were genotyped by PCR and FRLP. The prevalence of BsmI genotypes was 50% Bb, 23% bb, 27% BB in women and 48% Bb, 20% bb, 32% BB in men. The prevalence of FokI was 48% Ff, 22% ff, 30% FF in women and 50% Ff, 18% ff, 32% FF in men. The women bearing the rare allele b differ in homeostatic model assessment (HOMA) (p < 0.049) from women bearing common allele B, and the men differ in insulin level (p < 0.047) and HOMA (p < 0.017). There were no significant differences in anthropometric or biochemical parameters between genotypes in FokI in female and male groups. The common allele B is connected with biochemical risk factors of CVD in older Caucasian men and women.