| ObjectiveTo explore the relationship between Fok I, Apa I, Taq I polymorphisms in Vitamin D receptor gene(VDR) and lumbar disc herniation in Han population living in Tianjin. And to evaluate the association between Fok I, Taq I, Apa I polymorphisms and degenerative disc disease through meta-analysis. Subjects and Methods1.120 patients with lumbar disc herniation were recruited from the Second Hospital of Tianjin Medical University,Tianjin People's Hospital,Tianjin Hospital and General Hospital of Tianjin Medical University. At the same time, 120 healthy controls from Tianjin area were adopted. Magnetic resonance imaging scan of the lumbar spine was performed for all subjects. Trauma history of spine, scoliosis, spinal deformity, lumbar spinal stenosis, metabolic diseases and malignant tumors has been excluded. After signing informed consent, the basic parameters like age, height, weight from the volunteers are recorded. In addtion to that, genomic DNA was extracted from peripheral blood samples donated by every individual. The polymorphisms of Fok I?Apa I?Taq I in the vitamin D receptor from all the recruited were detected with use of SNap Shot.2. We performed a meta-analysis to analyze the association after searching the relevant case-control studies that examined the association of Fok I?Taq I and Apa I polymorphisms and degenerative disc disease through China National Knowledge Infrastructure(CNKI), Wanfang, Pub Med and EMBASE databases without restriction for language to identify available articles published up to now. Beyond that, we manually searched the references to acquire much more relevant papers. Critical inclusion, exclusion criteria and information table were made. Three authors carefully extracted and integrated valuable information from all eligible publications according to the criteria. Statistical analysis1. All data from our case-control study were processed by SPSS 20.0. The measurement data were expressed by ?x±s, enumeration data by number of cases or percentage. Differences of continuous variables between cases and controls in individual informations were assessed by evaluated by Student's t-test; categorical variables were assessed by chi-square test or Fisher test; Frequencies of alleles and genotypes of the two groups were compared by chi-square test., so does estimation of Hardy–Weinberg equilibrium. After adjusting age, sex and BMI, multivariate logistic regression was used to estimate odds ratios(ORs) and 95% confidence intervals(CIs) to assess the relationship between these polymorphisms and symptomatic lumbar disc herniation(p < 0.05 was considered statistically significant).2. All statistical tests and quantitative synthesis are conducted by STATA version 12.0(Stata Corporation, College Station, TX). Odds ratios(ORs) and 95% confidence intervals(CIs) as the main outcome measures were used to assess the strength of the association between Fok I, Taq I polymorphisms and lumbar disc degneration disease in different genetic model. The genetic model include: Fok I: allele comparison model(F vs. f), homozygote model(FF vs. ff), heterozygote model(Ff vs. ff), dominant model [(Ff+FF) vs. ff] and recessive model [FF vs.(ff+Ff)]; Taq I: allele comparison model(T vs. t), homozygote model(TT vs. tt), heterozygote model(Tt vs. tt), dominant model [(Tt+TT) vs. tt] and recessive model [TT vs.(tt+Tt)]; Apa I: allele comparison model(A vs. a),homozygote model(AA vs. aa),heterozygote model(Aa vs. aa),dominant model [(Aa+AA) vs. aa] ? recessive model [AA vs.(aa+Aa)]. Heterogeneity among the studies was evaluated with the chi-square-based Q test and I2 index(P < 0.10 was considered significant). I2 values of 25, 50, and 75 were normally reckoned low, moderate, and high heterogeneity. When the heterogeneity was present, the random-effect model was used to calculate the pooled OR, otherwise the fix-effect model was used. To explore the source of the heterogeneity, we also carried out the stratified analysis by ethnicity, age, sample size and regions of Europe for Fok I polymorphism, by ethnicity in all population, original country in Asia and sample size in Chinese for Taq I polymorphism and by country for Apa I polymorphism.In order to assess the stability of the results, we performed sensitivity analysis to evaluate the influence of the individual data on the overall effect by omitting each study sequentially. We utilized funnel plots to estimate the potential publication bias, in which the standard error of log(OR) of each study was plotted against its log(OR). Begg's and Egger's tests were also performed to assess the publication bias(P < 0.05 indicates a significant publication bias). Results 1. The features of clinical parametersCompared between case and control group in clinical information, no significant differences were found in age, gender, height, weight, smoking, drinking, hypertention and diabetes mellitus. But the BMI of two groups existed difference(P=0.014); Case group is 1.09Kg/m2 higher than control group in average. 2. The distribution of geneotype and allelesThe genotype frequencies of Fok I?Apa I?Taq I polymorphisms in control group are consistent with the Hardy–Weinberg equilibrium(P>0.05), representing the population well. There are no significant differences in the genotype and gene frequency of Fok I?Apa I?Taq I(P>0.05)?After adjustment of age, gender and BMI, logistic regression does not reveal that allele f?a?t were risk factors for the patients with lumbar disc herniation. 3. Meta-analysis: eveluating the Fok I polymorphism and degenerative disc diseaseA total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between Fok I polymorphism and degenerative disc disease in any genetic models(allelic model:OR=0.97, 95%CI=0.84-1.13,P=0.069; homozygote model :OR=0.98,95%CI=0.77-1.25,P=0.288; heterozygote model :OR=1.02,95%=0.81-1.30,P=0.296; dominant model : OR=0.99, 95%=0.79-1.24,P=0.433; recessive model:OR=0.96, 95%=0.74-1.24,P=0.005). In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype(OR=0.62, 95% CI=0.43-0.90, P=0.486) in age =40, and the F allele(OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype(OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype(OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype(OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. 4. Meta-analysis: eveluating the Taq I polymorphism and degenerative disc diseaseA total of 10 studies involving 1,220 cases and 1,225 controls were included in the present study. Overall, no evidence of significant risk between rs731236 polymorphism and degenerative disc disease was found in any genetic models(allelic model: OR=0.97, 95% CI=0.70-1.35, P=0.006; homozygote model: OR=1.01, 95% CI=0.63-1.63, P=0.958; heterozygote model: OR=1.11, 95%=0.69-1.81, P=0.990; dominant model: OR=1.14, 95%=0.72-1.79, P=0.753; recessive model: OR=0.93, 95%=0.63-1.38, P=0.003). In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by sample size( < 200) in Chinese population show that sample size may be the primary source of heterogeneity. 5. Meta-analysis: eveluating the Apa I polymorphism and degenerative disc diseaseTotally,3 studies involving 375 cases and 474 controls were included in the present study. The results of genetic models do not show any evidence of significant risk between Apa I polymorphism and degenerative disc disease(allelic model:OR=0.91, 95%CI=0.65-1.29, P=0.082; homozygote model : OR=0.76,95%CI=0.45-1.20, P=0.379; heterozygote model : OR=0.96, 95%=0.51-1.80,P=0.017;dominant model:OR=0.92,95%=0.52-1.65,P=0.005;recessive model: OR=0.83,95%=0.53-1.28,P=0.641).In addition,stratified analyses from different countries show that the researches in Chinese may be the primary source of heterogeneity.In addition to that,we do not find that Apa I polymorphism is the risk factor for different population in China and Japan. Conclusions1. The polymorphisms of Fok I?Apa I?Taq I may not be the independent risk factors for lumbar disc herniation risk of Han population in Tianjin.2. This meta-analysis suggested that the Fok I?Taq I?Apa I polymorphisms may not be associated with degenerative disc disease susceptibility. However, large-sample and well-designed case-control studies are still required to assess these polymorphisms and risk for degenerative disc disease. |
PDF Full Text Request