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Correlation 1.Runx2 Gene Polymorphism And Osteoporosis 2.Cystatin Clinical Application C And EGFR Estimating Equations GFR Evaluation

Posted on:2014-11-18Degree:MasterType:Thesis
Country:ChinaCandidate:X Y ZhangFull Text:PDF
GTID:2264330401466357Subject:Clinical laboratory diagnostics
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Objective Runx2gene is a key gene for bone formation, regulating the osteoblast’s development, differentiation, and bone formation. The purpose of this study is aimed to explore the relationship between Runx2gene polymorphism and osteoporosis. The study could also serve as a scientific basis for further study of the pathogenesis of osteoporosis.Methods Sampling120healthy objects, whom have been determined by healthy physical examination in the first affiliated hospital of Kunming medical university as Han population, and126from Yunnan Honghe Hani region population as Hani population. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyzing the Runx2gene promoter (P1)-330G/T allele polymorphism sites. The TaqMan SNP genotyping was used to analysing Runx2gene promoter (P2)-1025T/C allele polymorphism sites and sequencing of validation for the genotypes. Calcaneal quantitative ultrasound instrument was used to measure the bone mineral density of the study populations. Data analysis was performed by using SPSS17.0statistical software package. Anthropometric parameters and bone mineral density measurement data showed as mean±standard deviation. Using frequency count method for Gene frequency; Using the chi-square test for Hardy-Weinberg equilibrium analysis, in order to compare Han and Hani populations. Using Logistic regression analysis for osteoporosis, non-osteoporosis, and the relationship between influencing factors in Hani population. Using ANOVA or independent sample T-test for factors screening.0.05was used as the cut off value to determine the significance.Results1. HWE p-value by Hardy-Weinberg equilibrium analysis of Han and Hani populations were>0.05. Alleles are in line with the Hardy-Weinberg equilibrium The selected crowds are in line with Mendelian law of averages and representative.2. Chi-square test showed that between Han and Hani populations, the distribution of GG, GT, and TT genotypes and allele frequency of G, T on Runx2gene P1-330G/T polymorphism site had no significant difference (P>0.05). The distribution of TT, TC, and CC genotypes and allele frequency of G, T on Runx2gene P2-1025T/C polymorphism site had no significant difference (P>0.05).3. Analysis of variance (ANOVA) and independent-sample t test showed that in the normal BMD and low BMD groups of Hani population, the differences between Runx2gene (P1-330G/T) GG and GT genotypes and Runx2gene (P2-1025T/C) TT and TC genotypes were significant (P=0.000,<0.05);The differences between gender, height, weight was not statistical significant (P>0.05).4. Logistic regression analysis showed that in Hani population, the Runx2gene P1-330(G/T) site unrelated with BMD (OR>1,95%CI:0.649-2.756); Age is a risk factor for BMD (OR>1,95%CI:1.041-1.163). Runx2gene P2-1025(T/C) site maybe a BMD protection factor (OR<195%, CI:0.024-0.710).5. Compared with the researches by scholars in Spain and South Korea, genotype distributions and allele frequencies on Runx2gene P1-330and P2-1025polymorphism sites on the study population of Kunming Han and Honghe Hani in Yunnan Province shows no regional differences.Conclusions1. Runx2gene P1-330and P2-1025sites polymorphism exist in study populations.2. The genotype distributions and allele frequencies of Runx2gene P1-330G/T and P2-1025G/T polymorphism sites shows no significant difference in Kunming Han and Honghe Hani populations in Yunnan Province.3. The genotype distributions and allele frequencies of Runx2gene P1-330G/T and P2-1025G/T polymorphism sites shows significant difference in normal BMD and low BMD groups of Hani population in Yunnan Province.4. View of currently investigating cases, age is a risk factor for BMD, Runx2gene P1-330(G/T) site unrelated with BMD, Runx2gene P2-1025(T/C) site maybe a BMD protection factor, and the T allele gene of this site maybe a protective allele of BMD.5. Runx2gene can be looked as an osteoporosis candidate gene for predicting the risk of osteoporosis.6. The genotype distribution and allele frequencies of Runx2gene P1-330and P2-1025 sites polymorphism of the study population in Kunming Han, Honghe Hani Yunnan Province and Spain and South Korea shows no regional differences. Objective It’s increasingly important to diagnose chronic kidney disease (CKD) early for CKD became a global health important public health problem threaten to human after cardio-cerebrovascular diseases, cancer and diabetes. CystatinC can be freely filtrated through the glomerular, without renal tubular reabsorption and secretion. Thus it can be used as an ideal ndicator reflecting glomerular filtration rate. The purpose of this study was to investigate the clinical value of Cystatin C and eGFR estimating equation in GFR evaluation, to provide a scientific proof for early diagnosis and prevention of CKD.Methods According to the diagnostic criteria for CKD, randomly selected137patients of different GFR levels, various types of kidney disease in Nephrology, including71males, aged from15to77years old,66females, aged13to80years old. Take99mTc-DTPA renal dynamic imaging method as the "gold standard" for evaluation of GFR. The serum Cystatin C, serum creatinine, serum urea, urine micro total protein and urinary microalbumin were determined. The age, gender, height, weight and other anthropometric parameters Were recorded. In accordance with the detection indicators and measurement results, eGFR estimating equation was used to calculate the eGFR values. The above data were analyzed with SPSS17.0statistical software package, the correlation between each index with99mTc-DTPA GFR useing Pearson correlation analysis, showing with correlation coefficient r;99mTc-DTPA GFR<80ml/min boundaries point as the basis to determine glomerular filtration rate for calculating the area under ROC curve (AUC), and then compared with the0.5reference line the indicators for assessment of the diagnostic level; Z values calculated by hand, and comparison between AUC, Z>1.96(α=0.05); P<0.05, differences have statistical significance; estimation equation eGFR with99mTc-DTPA GFR comparison using linear regression analysis, and analysis of variance contains the constant term of each of the linear regression equation parameters for significant test, P<0.05, regression equation was statistically significant.Results1. Cys C, Urea, Scr with99mTc-DTPA GFR was negatively correlated (P<0.05), statistically significant; Utp, Ucr, Ualb, Ualb/Ucr with99mTc-DTPA GFR was absence of correlation, P>0.05, was not statistically significance; eGFR and CCR, Ucr/Scr with99mTc-DTPA GFR was positively correlated, P<0.05, statistically significant.2. Compare the area under the curve (AUC) of CC-EGFR, CG-eGFR MDRD-eGFR, rule-EGFR, LB-EGFR with0.5reference line, P<0.01, the difference was statistically significant. CC-EGFR compared with CG-eGFR, Z<1.96(α=0.05), P>0.05, AUC difference was not statistically significant; CC-EGFR compared with MDRD-eGFR, RULE-eGFR and LB-eGFR, Z>1.96(α=0.05), P<0.05, AUC difference was statistically significant.3. The eGFR with99mTc-DTPA GFR linear regression equation significant test, P<0.05, all the regression equation were statistically significant.4. Take95%confidence level, Cys C, SCR Urea, Ccr, CG-eGFR, MDRD-eGFR, rule-EGFR the LB-EGFR, CC-EGFR the cut-off value were0.83mg/1(sensitive sex92.4%, specificity100%),50.85umol/1(sensitivity91.7%, specificity100%),4.00mmol/1(sensitivity89.4%, specificity100%),83.85ml/min (sensitivity80.0%, specificity71.2%),114.55ml/minl.73m2(sensitivity100%, specificity85.6%),149.35ml/minl.73m2(sensitivity100%, specificity92.4%),95.1ml/minl.73m2(sensitivity100%, specificity92.4%),98.0ml/min1.73m2(sensitivity100%, specificity92.4%),142.15ml/min1.73m2(sensitivity100%, specificity95.5%).Conclusions1. Cys C is the most sensitive endogenous marker for GFR evaluation, conducive to improve the early diagnosis of chronic kidney disease.2. The eGFR estimating equation is the correct way to assess GFR, suitable for clinical application. Chinese subject group of eGFR estimating equation shows the most diagnostic value for GFR evaluation in this study. 3. Cys C and Scr joint detection is conducive to improve the accuracy and reliability of the GFR evaluation.
Keywords/Search Tags:Runx2gene, osteoporosis, bone mineral density, polymorphism, alleleGlomerular filtration rate, 99mTc-DTPA renal dynamic imaging, Cystatin C, Estimating equation
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