广州地区绝经后妇女维生素D受体基因多态性与骨密度关系的研究

目的：了解广州地区绝经后妇女维生素D受体基因多态性的分布，并进一步研究其与骨密度的关系。 方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFCP）等生物学技术检测203例绝经后广州地区妇女维生素D受体(VDR)基因型，同时用双能X线骨密度测量仪检测腰椎、股骨颈、瓦氏三角、大转子处骨密度（BMD）。 结果：203例受试对象中，VDR基因型分别为BB型17例（占8.3%）、Bb型60例（占29.6%），bb型126例（占62.1%）， b等位基因频率为76.85%、B等位基因频率为23.05%，基因型分布符合Hardy-Weinberg定律。分析其基因型与骨密度的关系显示：只有bb与Bb、BB基因型在腰椎骨密度存在差异（P<0.05）、Bb与BB的腰椎BMD无差异（P>0.05），其余部位3种基因型骨密度无差异（P>0.05）。 结论： VDR基因型与BMD间存在着一定关联，但尚不能作为预测广州绝经后妇女发生骨质疏松危险性的遗传标志。     

我国汉族儿童维生素D受体基因多态性分布

目的　了解我国汉族儿童维生素D受体 (VDR)基因多态性分布。方法　利用限制性内切酶BsmⅠ ,采用聚合酶链反应限制性片段长度多态性技术 (PCR -RFLP) ,对 1 69名健康汉族儿童进行了VDR基因分型 ,并计算其基因型频率分布。结果　中国汉族儿童VDR基因bb、Bb、BB基因型分别为 91 1 2 %、7 1 %、1 77%,明显不同于高加索人种 ,与韩国人较为相似。结论　VDR基因多态性具有种族差异性     

Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis

Vitamin D receptor (VDR) genotypes have been shown to be associated with differential susceptibility or resistance to tuberculosis. The influence of FokI, BsmI, ApaI and TaqI variants of VDR gene on 1, 25(OH)₂ D₃ modulated granzyme A expression of cytotoxic lymphocytes induced by culture filtrate antigen (CFA) of Mycobacterium tuberculosis was studied in 40 pulmonary tuberculosis (PTB) patients and 49 normal healthy subjects (NHS) by flow cytometry. In both the study groups, addition of 1, 25(OH)₂ D₃ (10^− 7M) significantly reduced the percentage of granzyme A positive cells in both unstimulated (NHS, p < 0.0001; PTB, p = 0.02) and stimulated culture conditions (CFA, NHS, p < 0.0001; PTB, p = 0.0001) which correlated positively with the IFN-γ levels (unstimulated, p = 0.01; CFA stimulated, p = 0.004) in NHS. The ApaI aa genotype and bbaaTT extended genotype were associated with a significantly decreased percentage of granzyme A positive cells in NHS (p < 0.05). Our results suggest that 1, 25(OH)₂ D₃ suppresses granzyme A probably by down-regulating Th1 cytokine response. Moreover, the VDR gene variants might regulate cytotoxic T-cell response via 1, 25(OH)₂ D₃ mediated suppression of granzyme A expression in tuberculosis.     

Identification of a novel Tru9 I polymorphism in the human vitamin D receptor gene

We found a novel Tru9 I restriction polymorphism in intron 8 of the vitamin D receptor (VDR) gene in healthy French Caucasians. It corresponds to a substitution of A for G at nucleotide +443 bp from the end of exon 8. The allelic frequency of G and A in 151 unrelated subjects was 0.894 and 0.106, respectively. This polymorphism is located in the reverse primer binding site of primers that have been frequently used in the literature to genotype a BsmI restriction polymorphism. The presence of the Tru9I A allele may result in allele drop-out when the BsmI restriction fragment length polymorphism (RFLP) is genotyped with the original set of primers. This novel Tru9I polymorphism may be useful for analysis of the VDR gene. Received: August 2, 1999 / Accepted: September 21, 1999     

维生素D代谢相关基因多态性研究进展

维生素D缺乏是佝偻病的主要病因,遗传因素在其发生发展中的作用正逐渐受到重视.与维生素D代谢相关的基因包括:维生素D受体基因(vitamin D receptor,VDR)、维生素D结合蛋白基因(vitamin D-binding protein,DBP)、细胞色素P450基因(cytchrome P450,CYP)、NADSYN1/DHCR7基因.该文就这些基因多态性与维生素D代谢关系的进展作一阐述.

Abstract：

The major cause of tickets is Vitamin D deficiency.Genetic factors contributing to the pathogenesis of rickets have been investigated with more and more attention.Genes related to vitamin D metabolism include:VDR gene,DBP gene,CYP gene and NADSYN1/DHCR7 gene.In this article,we review the current status and progress in gene polymorphisms and their association with vitamin D metabolism.     

维生素D受体基因多态性与乳腺癌的相关性

目的：研究维生素D受体基因的多态性与乳腺癌的关系。方法：收集86例乳腺癌患者及134名对照,用聚合酶链反应－限制性片段长度多态性方法,在维生素D受体基因的3’端分析了两个限制性酶切位点（ApaI及TaqI）的多态分布。结果：发现TaqI位点等位基因在两个群体间分布的差异有显著性（P＝0．0004）。进一步对基因型进行分析发现,Tt、tt基因型与乳腺癌相关。而ApaI位点两等位基因未发现在两群体中存在差异。对ApaI及TaqI两座位的单体型进行分析,发现tA间存在连锁不平衡。在两群体中分析单体型的分布发现tA在病例中的比例明显高于对照人群,提示tA单体型与乳腺癌相关。两个位点等位基因及单体型与临床指标的分析均未发现阳性结果。结论：维生素D受体基因的多态怀与乳腺癌有关,提示维生素D受体基因与乳腺癌有关。     

Association of the vitamin D receptor start codon polymorphism (FokI) with bone mineral density in postmenopausal Korean women

We undertook this study in order to examine the association between bone mineral density (BMD) and a polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene. This polymorphism was detected by restriction fragment length polymorphism analysis, using polymerase chain reaction (PCR) and the restriction endonuclease FokI. The f allele indicates the presence of the FokI site, and the F allele its absence. The FokI genotype was determined in 174 postmenopausal Korean women, aged 43–71 years. The distribution of FokI genotypes in Koreans was found not to differ significantly from those found in Caucasians and Japanese, although it does differ significantly from that found in the black American population. We observed a significant association between the FokI polymorphism and lumbar BMD; P = 0.048, analysis of covariance [ANCOVA], but no association with femoral neck BMD (P = 0.505, ANCOVA). Those with the ff genotype had a 13.3% lower BMD in the lumbar spine than the FF subjects. In addition, a significantly higher prevalence of the ff genotype was observed in osteoporotic compared with osteopenic or normal women (P = 0.036, χ² test). These data suggest that the ff genotype of the VDR gene correlates with decreased BMD in the lumbar spine in postmenopausal Korean women. Received: May 8, 2000 / Accepted: June 7, 2000     

阿昌族与汉族维生素D受体基因Fok多态性

目的　了解维生素 D受体基因多态性在中国不同民族中的分布。方法　应用聚合酶链反应 -限制性片段长度多态性分析、基因测序等技术检测 6 8名阿昌族人和 92名汉族人的维生素 D受体基因Fok 多态性 ,比较两组维生素 D受体基因型和等位基因的分布频率。结果　在 6 8名阿昌族人中 FF基因型占 18%、Ff基因型占 35 %、ff基因型占 4 7% ,而在 92名汉族人中 FF基因型占 2 2 %、Ff基因型占 5 2 %、ff基因型占 2 6 %。两组维生素 D受体基因型的分布频率差异有显著性 (χ2 =7.716 ,P=0 .0 2 1)。结论　阿昌族与汉族维生素 D受体基因 Fok 多态性分布频率差异有显著性。     

Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans

1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinson's disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.     

维生素D受体基因ApaⅠ和TaqⅠ位点多态性与帕金森病的相关性研究

目的 探讨维生素D受体(vitamin D receptor,VDR)基因ApaⅠ和Taq Ⅰ位点多态性与帕金森病(Parkinson's disease,PD)遗传易感性的相关性.方法 采用聚合酶链反应-限制性片段长度多态性技术和基因测序方法,检测285例中国北方汉族散发PD患者与285名正常对照VDR基因ApaⅠ和TaqⅠ位点多态性,并比较两组基因型和等位基因频率的差异.结果 ApaⅠ和Taq Ⅰ位点基因型和等位基因频率在PD组和对照组之间差异均无统计学意义(P＞0.05).将样本按性别及发病年龄分组后比较,ApaⅠ位点各亚组间基因型频率和等位基因频率差异亦无统计学意义(P＞0.05),而TaqⅠ位点的基因型分布在男性PD组(168例)与男性对照组(1 60名)之间差异有统计学意义(x2=4.187,P=0.032,OR=2.149,95％CI:1.011～4.567),男性PD组T等位基因频率较男性对照组显著增高(x2=3.867,P=0.036,OR=2.064,95％CI:0.989～4.307).结论 VDR基因ApaⅠ位点多态性与PD风险间无相关性,但TaqⅠ可能是男性PD的风险因素.     

Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.     

维生素D受体基因多态性与骨关节炎关系的Meta分析

背景:维生素D受体与骨关节炎存在密切联系,而维生素D受体基因多态性被认为能够调控维生素D受体,进而影响骨关节炎的发生,但现有的研究仍存在争议。目的:确认维生素D受体基因多态性与骨关节炎的关系。方法:系统检索PubMed、Web of Science、EMbase、Cochrane Library、中国生物医学文献数据库、中国学术期刊全文数据库、万方、维普等数据库,检索时限均为建库截至2019年10月,检索所有提供了骨关节炎患者和非骨关节炎患者维生素D受体基因(ApaI、Bsm I、TaqI和Fok I)多态性数据的病例对照研究,采用Stata 14.0统计软件进行分析。结果与结论:①总共纳入21篇相关研究,共7 109例患者,其中包括骨关节炎患者3 123例,非骨关节炎患者4 006例;②Meta分析显示,欧洲人维生素D受体Bsm I多态性与骨关节炎之间存在相关性[(BB vs. bb:OR=1.677,95%CI(1.051,2.676),P=0.030;BB vs. Bb+bb:OR=1.780,95%CI(1.175,2.697),P=0.007],但只有3篇研究;亚洲人维生素D受体FokI多态性与骨关节炎之间存在相关性[(FF vs. Ff+ff:OR=0.609,95%CI(0.410,0.907),P=0.015],只有3篇研究;维生素D受体TaqI和ApaI多态性与骨关节炎无显著相关性,在排除异质性后结果也无明显相关性;③结果表明,维生素D受体ApaI、Bsm I、TaqI和FokI多态性可能与骨关节炎无明显相关性。     

Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Genetic alterations in the vitamin D receptor gene (VDR) may lead to important defects in gene activation that principally affect immune function. We have hypothesized a possible relationship between endometriosis and/or infertility and the VDR polymorphisms (ApaI, TaqI, FokI, and BmsI). The study was a case-control study including 132 women with endometriosis-related infertility, 62 women with idiopathic infertility, and 133 controls. VDR polymorphisms were studied by restriction fragment length polymorphism. We found relatively similar VDR polymorphism genotype frequencies in cases and controls. When patients with minimal/mild and moderate/severe endometriosis were studied separately, no difference was found. When we compared infertile groups with and without endometriosis there was no statistically significant difference. The data suggest that VDR polymorphisms did not play an important role in the pathogenesis of endometriosis and/or infertility in the Brazilian women studied.     

Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine

The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies.     

Polymorphisms at the ligand binding site of the vitamin D receptor gene and osteomalacia

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p=0.08). Also no association between biochemical data and VDR gene polymorphisms was observed.     

中国汉族和维吾尔族MRC1基因多态性与肺结核病的相关性

目的 探讨中国汉族和维吾尔族人群MRC1基因多态性与肺结核病易感性的联系. 方法 应用PCR和DNA测序技术,对中国汉族454例和维吾尔族595例人群的MRC1基因的第7号外显子6个SNPs(G1186A、G1195A、T1212C、C1221G、C1303T和C1323T)基因型及基因频率分布进行检测,并进行连锁不平衡分析. 结果 中国汉族人群中G1186A位点等位基因G型分布频率在肺结核病组和正常健康组之间存在显著差异(P =0.037;OR =0.76;95％ CI:0.58～0.98);AG基因型在两组之间存在显著性差异(P ＜0.01;OR=0.57;95％ CI:0.37 ～0.87).在年龄和性别校正后,G1186A位点在显性(P＜0.01;OR=0.59;95％ CI:0.40～0.87)、超显性(P =0.045;OR =0.69;95％ CI:0.47～0.99)和加性模式(P =0.041;OR=0.76;95％ CI:0.59 ～0.99)时,与肺结核病存在显著相关性.在维吾尔族人群中G1186A位点的等位基因G的分布频率在两组之间的分布具有显著性差异(P =0.031;OR=1.29;95％CI:1.02 ～ 1.62);基因型分析发现AA基因型在两组之间也存在显著性差异(P=0.033;OR=1.64;95％ CI:1.04～2.60);在年龄和性别校正后,G1186A位点在加性模式下与肺结核病存在相关性(P=0.033;OR=1.28;95％ CI:1.02～1.61).连锁不平衡分析发现,构建的单体型GGTCCT(P=0.032;OR =0.75;95％ CI:0.57 ～0.97)和GGTCCC(P=0.044;OR=0.57;95％ CI:0.33 ～0.99)与肺结核病存在显著的相关性. 结论 MRC1基因G1186A位点与中国人群肺结核病相关.     

Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese

Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4+T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and type 1 diabetes. However, this issue is still controversial; therefore, we examined this gene polymorphism in a large number of type 1 diabetic patients as a multi-center collaborative study in Japan. A total of 1,373 subjects, including 774 cases and 599 control subjects of Japanese origin, were studied. The frequency of carriers of the BB genotype in type 1 diabetic patients was significantly higher than that in controls (p<0.01, odds ratio 3.65). Moreover, IFN-gamma production upon anti-CD3 stimulation in the BB genotype group was significantly higher than that in the Bb and bb genotype groups (p<0.05), suggesting that the polyclonal T cell response in BB genotype patients is Th1 dominant. Based upon these results, we propose that it may be worthwhile to focus on subjects with the BB genotype of this gene polymorphism as having high risk for type 1 diabetes.     

The vitamin D receptor FokI start codon polymorphism and bone mineral density in osteoporotic postmenopausal French women

This study examined the association between bone mineral density (BMD) and a T/C polymorphism in the first of the two initiation codons in the vitamin D receptor (VDR) gene. The polymorphism was detected using the restriction enzyme FokI, the F allele indicating absence of the first codon and the f allele its presence. The FokI genotype was determined in 124 postmenopausal osteoporotic French women who were 45-90 years old. The distribution of FokI genotypes in the osteoporotics did not differ significantly from that found in a control group. There were no significant differences by FokI genotype groups in our total sample of osteoporotic women for age, years since menopause, height, weight, and BMD at lumbar spine and femoral neck. However, when only those patients under the age of 75 years are analysed (98 subjects), those with the ff genotype (10% of the population) had a significantly lower BMD at the femoral neck than FF and Ff subjects. This suggests that the ff genotype of the VDR gene correlates with decreased BMD at the femoral neck in French postmenopausal women.