骨桥蛋白基因多态性与特发性草酸钙结石的相关性研究

发布时间：2018-06-15 15:52

本文选题：骨桥蛋白 + 基因多态性　；参考：《南昌大学》2014年硕士论文

【摘要】：目的：探讨骨桥蛋白（osteopontin，OPN）基因多态性与江西赣南地区特发性草酸钙结石（idiopathic calcium oxalate stones，ICS）的相关性。方法：收集2012年7月至2013年12月江西赣南地区218例ICS患者（ICS组）和同期187例正常人群（对照组）外周血液及部分研究对象尿液标本。采用Logistic回归模型分析ICS形成的影响因素，，如年龄、性别、身体质量指数（bodymass index，BMI）以及尿液和血液生化指标等；实时荧光定量聚合酶链式反应（real-time polymerase chain reaction，Real-time PCR）TaqMan-MGB探针法检测OPN基因rs6840362、rs6532040和rs11439060位点单核苷酸多态性（singlenucleotide polymorphism，SNP），分析OPN基因型和单体型与ICS的相关性。结果：单因素分析显示，ICS组BMI和尿液钙离子浓度显著高于对照组，而尿液PH值和每日液体摄入量显著低于对照组（P0.05）。进一步对上述影响因素行Logistic回归分析，发现尿液钙离子浓度在两组间的差异仍具有统计学意义（P=0.000）。两组人群中，OPN基因三个位点基因型频率分布均符合Hardy-Weinberg平衡定律。rs11439060位点，ICS组和对照组delG、G等位基因频率分别为:69%、31%和57%、43%，差异具有统计学意义（P=0.000）；ICS组和对照组delGdelG、delGG和GG基因型频率分别为45.9%、46.3%、7.8%和32.1%、49.7%，18.2%，以GG基因型为参照，两组间delGdelG和delGG基因型差异有统计学意义（P=0.000，OR=3.333，95%CI=1.715~6.478和P=0.017，OR=2.172，95%CI=1.138~4.147）。rs6840362位点，ICS组和对照组C、T等位基因频率分别为:91.7%、8.3%和95.7%、4.3%，差异具有统计学意义（P=0.021）。rs6532040位点，ICS组和对照组A、G等位基因频率分别为:90.1%、9.9%和94.4%、5.6%，差异具有统计学意义（P=0.026）。rs6840362和rs6532040位点基因型两组间差异无统计学意义（P0.05）。各基因型与临床表型的相关性分析，差异无统计学意义（P0.05）。OPN基因单体型分析显示，C-G-delG单体型与ICS的形成呈正相关（OR=6.326，95%CI=1.958~20.442），C-A-G与ICS的形成呈负相关（OR=0.600，95%CI=0.448~0.804）。结论： 1. OPN基因多态性与赣南地区ICS形成显著相关。其中携带rs11439060位点delGdelG、delGG基因型和C-G-delG单体型个体患ICS的风险较高；而携带rs11439060位点GG基因型和C-A-G单体型个体患ICS的风险较低。 2.尿液钙离子浓度增加可能是ICS形成的危险因素。
[Abstract]:Objective: to investigate the association between osteopontinin (OPN) gene polymorphism and idiopathic calcium oxalate stone (calcium oxalate) in southern Jiangxi province. Methods: from July 2012 to December 2013, the peripheral blood fluid and urine samples of 218 patients with ICS in Gannan area of Jiangxi Province and 187 normal controls (control group) were collected. Logistic regression model was used to analyze the influencing factors of ICS formation, such as age, sex, body mass index (BMI), urine and blood biochemical indexes. Real-time polymerase chain reactionation real-time PCR TaqMan-MGB probe method was used to detect rs6840362 rs6532040 and single nucleotide polymorphisms of rs11439060 locus (SNPs 6532040). The correlation between rs11439060 genotype and haplotype was analyzed. Results: univariate analysis showed that BMI and urine calcium concentration in ICS group were significantly higher than those in control group, while urine PH value and daily fluid intake were significantly lower than those in control group (P 0.05). Logistic regression analysis of the above factors showed that the difference of urine calcium concentration between the two groups was still statistically significant. The genotype frequencies of three sites of OPN gene in the two groups were in accordance with Hardy-Weinberg equilibrium law. The allele frequencies of delGnG in the ICS group and the control group were 31% and 57%, respectively. The difference was statistically significant (P < 0. 000). The genotype frequencies of delGG and GG in ICS group and control group were 45.9% and 46.8% and 32.1%, respectively. There were significant differences between the two groups in the genotype frequencies of CT alleles in the delGdelG and delGG genotypes. The frequencies of CT alleles were 91.773% in ICS group and 9.3% in control group, respectively. The difference was statistically significant. The frequency of CT alleles in ICS group and control group was 90.1% and 9.9% respectively, and the frequency of CT allele was 91.773% in ICS group and 9.9% in control group. There was a significant difference between the two groups. There was a significant difference in the frequency of CT alleles between the two groups (P = 3.33395). The frequencies of CT alleles in the ICS group and the control group were 90.1% and 9.9%, respectively, and the frequencies of CT alleles in the ICS group and the control group were 90.1% and 9.9%, respectively. There was no significant difference between the two groups (P < 0.05) and the genotype of rs6532040 locus (P < 0.05). There was no significant difference between the genotype and clinical phenotype. The haplotype analysis of C-G-delG gene showed that there was a positive correlation between C-G-delG haplotype and the formation of ICS. There was a negative correlation between C-A-G and the formation of ICS. There was a negative correlation between C-G-delG haplotype and the formation of ICS, and there was a negative correlation between C-G-delG haplotype and the formation of ICS. Conclusion: 1. OPN gene polymorphism was significantly associated with ICS formation in southern Jiangxi. Among them, the individuals carrying rs11439060 locus delGdelGG genotype and C-G-delG haplotype individuals had a higher risk of ICS, while those with rs11439060 locus GG genotype and C-A-G haplotype individuals had a lower risk of ICS. 2. An increase in urine calcium concentration may be a risk factor for the formation of ICS.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R691.4

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