维生素D及其受体基因多态性与类风湿关节炎关系的研究

目的 探讨淮海经济区汉族人群维生素D水平及其受体(VDR)基因多态性与类风湿关节炎(RA)的关系.方法 收集该地区无血缘关系的120例RA患者(RA组)和120名健康人(对照组)的全血标本,采用聚合酶链反应和限制性内切酶法(PCR-RFLP)研究VDR的Bsm Ⅰ 、ApaⅠ等位基因多态性与类风湿关节炎发病之间的关系,采用电化学发光法检测血清中维生素D含量,研究其与RA发病的关系.使用x2检验和t检验进行统计学分析.结果 RA组与对照组之间ApaⅠ酶切位点AA、Aa、aa基因频率的差异有统计学意义(x2=23.85,4.34,43.2,P值均＜0.05),Bsm Ⅰ酶切位点BB、Bb、bb基因频率的差异无统计学意义(P值均＞0.05).进一步分析VDR基因型与RA患者的性别及有无骨侵蚀的关系,发现VDR各基因型频率差异无统计学意义(P值均＞0.05).RA组维生素D水平显著低于对照组[(2.8±0.3)与(4.0±0.4) ng/ml],RA患者中骨侵蚀组维生素D水平显著低于无骨侵蚀组[(1.8±0.3)与(3.1±0.4)ng/ml],差异均有统计学意义(F=193.26,41.96,P值均＜0.05).但RA患者中男性患者组与女性患者组之间维生素D水平相当[(2.6±0.3)与(2.7±0.4) ng/ml],差异无统计学意义(P＞0.05).结论 VDR基因多态性ApaⅠ与淮海经济区汉族人群RA发病是显著相关联的,基因型AA、Aa的出现可能增加RA的易患性,基因型aa可能为RA的保护型基因,同时VDR各基因型与RA患者性别及是否存在骨侵蚀无相关性;血清维生素D水平下降与RA的发病及骨侵蚀的发生是显著相关的,与RA患者的性别无相关性.     

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.     

Seasonal and regional variations of asthma and association with osteoporosis: possible role of vitamin D in asthma

Background. Based on the evidence that vitamin D is involved in the development of immune system and vitamin D receptor gene is associated with asthma, we supposed that vitamin D is related to the development of asthma. Methods. Asthma patients were identified from the Swedish Hospital Discharge Register and the hospitalization rate was examined by different seasons and regions. Standardized incidence ratios (SIRs) for asthma were examined among patients hospitalized for osteoporosis compared with the general population. Results. A total of 172,384 patients were hospitalized for asthma in Sweden during 1965–2007. More patients were hospitalized in winter and North Sweden than in summer and South Sweden. The risk of asthma after osteoporosis was significantly increased, giving an overall SIR of 2.93. The risk was higher in male patients when compared with female subjects. Patients hospitalized for osteoporosis at age younger than 55 showed a high risk. Reversing the analyses and examining the risk of osteoporosis after hospitalization of asthma, SIR was significantly increased (3.54). Conclusion. Our study suggests that vitamin D, as indicated by the high risk of asthma after osteoporosis and the seasonal and regional variations of hospitalization, could play an important role for the development of asthma.     

维生素D受体基因多态性与慢性乙型肝炎的相关性

目的探讨维生素D受体（VDR）基因多态性与慢性乙型肝炎的相关性。方法以53例慢性乙肝患者和56例健康人为研究对象,应用聚合酶链反应-限制性片段长度多态性方法分析VDR基因FokⅠ和BsmⅠ酶切位点的多态性。两组间基因型比较采用x^2检验。结果53例慢性乙肝患者中,BB、Bb、bb基因型频率分别为9．4％、20．8％、69．8％,其中BB基因型频率高于正常对照组,差异有统计学意义（P〈0．05）。B等位基因频率在慢乙肝组为19．8％显著高于正常对照组8．9％（P〈0．05）。病例组中FF、FT、ff基因型频率分别为32．1％、52．8％、15．1％,与正常对照组无统计学差异。F等位基因频率在慢乙肝组为58．5％,与正常对照组差异无统计学意义。结论VDR基因多态性与HBV感染有关,特别是Bsml酶切位点多态性可增加慢性HBV感染。     

维生素D受体基因型与骨密度的关系

目的　了解维生素D受体 (VDR)基因的BsmI多态性在中国人群中的分布 ,并进一步探讨其与骨密度 (BMD)的关系。方法　应用聚合酶链反应 -限制性片断长度多态性解析 (PCR RFLPs)技术检测了 1 86例在长春地区生活 1 0年以上的无亲缘关系的绝经前健康汉族女性VDR基因型 ,用双能X线骨密度仪 (DEXA)测腰椎BMD ,同时考察它们之间的关系。结果　VDR基因型分布频率为Bb:2 3例 (1 2 .4% ) ,bb :1 63例(87.6 % ) ,BB型缺如。b等位基因在本组人群中分布高达 93 .8%。各型的BMD值分别为 :Bb型 (1 .1 87± 0 .0 88) g/cm2 ,bb型 (1 .1 53± 0 .1 1 2 ) g/cm2 ,两组比较差异无统计学意义 (P >0 .0 5)。结论　中国长春地区绝经前汉族女性的VDR基因的BsmI多态性与骨密度间无相关关系。     

维生素D受体基因多态性与酒精性肝病的相关性

目的: 探讨维生素D受体(vitamin D receptor,VDR)基因多态性与酒精性肝病易感性之间的关系.方法: 采用半巢式聚合酶链式反应-限制性片段长度多态性(semi-nested PCR-RFLP)技术检测50例酒精性肝病患者和72例健康志愿者VDR多态性的基因型, 并比较甘肃汉族人群和酒精性肝病患者之间VDR基因多态性、基因型频率、等位基因频率的差异与酒精性肝病相关性的分析.结果: 共检出3种VDR基因型, 即BB、Bb、b b. 病例组b b基因型频率显著高于对照组(χ2 = 7.16, P = 0.028, OR = 2.698, 95% CI:1.167-6.235); b等位基因的频率病例组显著高于对照组(χ2 = 11.64, P = 0.001, OR = 3.071,95% CI: 1.583-3.958). 通过多因素非条件Logistic回归模型, 发现携带bb基因型的个体暴露于酒精后容易发展成酒精性肝病, bb基因型可能是酒精性肝病发生的一种易患因素( OR = 2.272, OR 95% CI: 0.971-5.318).结论: 维生素D受体基因BsmⅠ酶切位点基因型与酒精性肝病之间存在相关性, bb基因型可能是酒精性肝病发生的一种易患基因.     

Association between vitamin D receptor gene BsmI,FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus: a meta-analysis

Association studies of vitamin D receptor (VDR) gene polymorphisms and the risk of systemic lupus erythematosus (SLE) have yielded conflicting results in different backgrounds. We aimed to evaluate the association between VDR gene polymorphisms and SLE risk. A predefined electronic databases search was performed to identify eligible studies that were related to the association of VDR gene BsmI, FokI, ApaI or TaqI polymorphism with SLE risk. Either a fixed-effects model, or in the presence of heterogeneity, a random-effects model was used to calculate the pooled odds ratios (ORs) and its corresponding 95 % confidence interval (CI). A total of 11 studies with 1,621 cases and 1,883 controls were included in this meta-analysis. BsmI B allele was associated with the onset of SLE for overall populations (OR 1.726, 95 % CI 1.214–2.455) and Asians (OR 1.952, 95 % CI 1.135–3.355). FokI FF genotype was correlated with the susceptibility of SLE for Asians (OR 1.469, 95 % CI 1.005–2.148). FokI T/C and TaqI polymorphisms were not associated with SLE risk for Caucasians. There was no significant association between ApaI polymorphism and SLE risk for overall populations, Asians and Caucasians. No evidence of publication bias was observed. In conclusion, BsmI B allele may be a risk factor for SLE onset among overall populations and Asians, and FokI FF genotype is a risk factor for SLE susceptibility in Asians. However, more studies should be performed in the future.     

Correlation between polymorphism of vitamin D receptor TaqI and susceptibility to tuberculosis: An update meta-analysis

Background:To investigate the association between TaqI polymorphism of the vitamin D receptor gene and tuberculosis (TB).Methods:A systematic search was performed in PubMed, Embase, Web of Science, Elsevier Science Direct, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases for case-control study on TaqI gene polymorphism and TB susceptivity. Quality assessment of studies was performed using the Newcastle–Ottawa Scale for the methodological assessment of case-control studies, and R 4.0.5 software was used for the meta-analysis.Results:Among the 243 selected articles, 27 in the meta-analysis. The meta-analysis showed that the TaqI gene polymorphism allene gene model (t vs T, odds ratio [OR]: 1.12, 95% confidence interval [CI]: 0.99–1.27); dominant model (tt + tT vs TT, OR: 1.12, 95% CI: 0.98–1.29); recessive model (tt vs tT + TT, OR: 1.25, 95% CI: 1.03–1.51); codominant A (tt vs TT, OR: 1.37, 95% CI: 1.00–1.87); codominant B (tT vs TT, OR: 1.09, 95% CI: 0.99–1.19). And subgroup dominant model (tt + tT vs TT, OR: 1.27, 95% CI: 1.03–1.55) in Indianas, recessive model (tt vs tT + TT, OR: 1.49, 95% CI: 1.05–2.11) in Iranians, co-dominant B (tT vs TT, OR: 1.28, 95% CI: 1.03–1.59; OR: 1.42, 95% CI: 1.05–1.93) in Indianas and Iranians.Conclusion:This meta-analysis suggests a significant association between TB and the risk of TaqI in Iranians and Indians, but the vitamin D receptor polymorphism TaqI was not associated with Chinese. Thus, validation studies will be required to confirm these findings.     

Vitamin D receptor gene polymorphisms and colorectal cancer risk: a systematic meta-analysis

AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.     

Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis

The aim of this study was to summarize published results on the association between vitamin D intake and the development of rheumatoid arthritis (RA) and between serum vitamin D levels and RA activity. Evidence of a relationship between vitamin D intake and the development of RA and between serum vitamin D levels and RA activity was studied by summarizing published results using a meta-analysis approach. Three cohort studies including 215,757 participants and 874 incident cases of RA were considered in this meta-analysis, and eight studies on the association between serum vitamin D levels and RA activity involving 2,885 RA patients and 1,084 controls were included. Meta-analysis showed an association between total vitamin D intake and RA incidence (relative risk (RR) of the highest vs. the lowest group?=?0.758, 95?% confidence interval (CI) 0.577?C0.937, p?=?0.047), without between-study heterogeneity (I ²?=?0?%, p?=?0.595). Individuals in the highest group for total vitamin D intake were found to have a 24.2?% lower risk of developing RA than those in the lowest group. Subgroup meta-analysis also showed a significant association between vitamin D supplement intake and RA incidence (RR 0.764, 95?% CI 0.628?C0.930, p?=?0.007), without between-study heterogeneity. All studies, except for one, found that vitamin D levels are inversely associated with RA activity. One study found no correlation between vitamin D levels and disease activity among 85 RA patients, but these patients had a high incidence of vitamin D deficiency, which might have influenced the study outcome. Meta-analysis of 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development. Furthermore, available evidence indicates that vitamin D level is associated with RA activity.     

Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis

Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results to date have been inconclusive. The aim of this study was to investigate the association between polymorphisms in the VDR gene and T1DM risk by meta-analysis. A total of 57 case-control studies in 26 published studies were included. The results indicated that the BsmI polymorphism is associated with increased risk of T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no significant association was found in other populations for other polymorphisms. Results from the current study suggest that the BsmI polymorphism is associated with increased risk of T1DM, especially in Asians. Further studies are needed to confirm our results.     

Association between vitamin D and hepatitis C virus infection: A meta-analysis

AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in 2011.Studies must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected individuals.The inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full papers.Due to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was used.Heterogeneity was assessed using I2statistics.The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.RESULTS:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D levels.Most of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 years.Four studies were conducted in human immunodeficiency virus/HCV infected individuals.Regarding vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/mL.With regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1.57;95%CI:1.12-2.2)and those supplemented with     

The relation between osteoporosis and vitamin D levels and disease activity in ankylosing spondylitis

In this study, the relation between osteoporosis and vitamin D and the disease activity in patients with ankylosing spondylitis (AS) was investigated. A hundred patients with AS and 58 healthy individuals were included in the study. In addition to the routine blood and urine tests, serum 25-(OH)D3, parathormone (PTH), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total calcium, ionized calcium, and phosphorous levels of all participants were also measured. Bone mineral density (BMD) measurements were performed at the anterior–posterior and lateral lumbar and femur regions. Anterior–posterior and lateral thoracic and lumbosacral radiography was performed on all participants. The disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional status by Bath Ankylosing Spondylitis Functional Index (BASFI), and mobility by Bath Ankylosing Spondylitis Metrology Index (BASMI). In the patient group, BMD values obtained from the lateral lumbar and femur regions and serum vitamin D levels were lower than the control group. A negative relation was determined between the lateral lumbar BMD values and ESR, CRP, and BASDAI scores of patients with AS. The ESR, CRP levels, and BASMI scores of the AS patients with osteoporosis were significantly higher, when compared to patients without osteoporosis. The negative correlation between serum 25-(OH)D3 level and ESR, CRP levels did not reach a statistically significant level in patients with AS; the positive correlation between PTH levels and ESR, and the negative correlation between CRP and BASDAI also did not reach a statistically significant level. Vitamin D deficiency in AS may indirectly lead to osteoporosis by causing an increase in the inflammatory activity. The present authors believe that it would be beneficial to monitorize vitamin D levels together with BMD measurements in order to determine the patients under osteoporosis risk.