rs13124007、rs6850166、rs2331142多态性与汉族女性痛风相关性研究

【作者】 张秀娟；

【导师】 李长贵；

【作者基本信息】 青岛大学 ， 内科学， 2012， 硕士

【摘要】 目的探讨rs13124007、rs6850166、rs2231142 3个SNP位点的基因多态性与中国汉族女性人群痛风易感性之间的相关性。方法采用Hardy-Weinberg平衡原则检测本实验随机选取的研究对象是否具备群体代表性。采用聚合酶链式反应(PCR技术),特异性扩增GLUT9基因和ABCG2基因中本实验所需要的目的片段。分别对目的片段进行测序后,比较痛风组和正常对照组的基因型频率及等位基因频率分布情况,并对女性痛风人群进行痛风易感基因的基因型-表型相关性分析。结果①痛风组年龄与正常对照组年龄相互匹配(P>0.05),痛风组的体重指数、腰臀比、收缩压、舒张压、血糖、血尿酸、甘油三酯、尿素氮和肌酐水平明显高于正常对照组(P<0.05),另外,女性痛风患者中15.45%合并有痛风石。②Rs13124007、rs6850166和rs2231142位点的基因多态性均与痛风的易感性相关。Rs6850166和rs2231142位点的基因型频率在两组间存在显著差异(P=0.011；P=0.001),且痛风组中这两个SNP位点的A等位基因频率均显著高于正常对照组(P=0.002,OR 2.31[95% CI 1.33—4.01]；P<0.001,OR 1.88[95% CI 1.35—2.62])。Rs13124007位点的基因型频率在两组间无统计学差异(P>0.05),但痛风组中该位点的C等位基因频率高于正常对照组(P=0.034,OR 1.73[95% CI 1.04—2.89])。③Rs13124007位点携带GG基因型、GC基因型及CC基因型的个体间表型无显著差异(P>0.05)。Rs6850166位点GG基因型的个体与GA基因型和AA基因型的个体比较,痛风合并肥胖的风险更大(P=0.026,OR 0.21[95% CI0.04-0.93]；P=0.041,OR 0.28[95%CI0.08-1.01])。Rs2231142位点携带AA基因型的个体较CC基因型的个体具有更高的腰臀比(P=0.047)；携带AA基因型及CA基因型的个体与携带CC基因型的个体相比,具有更高的收缩压(P=0.021)、尿酸浓度(P=0.037)、甘油三酯水平(P=0.038)及总胆固醇水平(P=0.012)；且携带AA基因型及CA基因型的个体与CC基因型的个体相比,合并高血压者及糖尿病者均较多(P=0.018,OR 0.26[95% CI1.17-6.08]；P=0.041,OR 3.62[95% CI 0.99-13.18])。结论Rs13124007(G/C)、rs6850166(G/A)、rs2231142(C/A)位点的基因多态性与中国汉族女性痛风易感性密切相关,rs2231142位点的A等位基因可能还与中国汉族女性痛风人群的血压、血糖、血脂水平相关。更多还原

【Abstract】 Objective:To investigate associations between gout and polymorphisms of rsl3124007, rs6850166, rs2231142 in Chinese Han females.Methods:Hardy-Weinberg was used to verify the representativeness of the sample. Specifically amplify the target fragments of GLUT9 gene and ABCG2 gene and genotyping was performed by polymerase chain reaction (PCR) technology. Forther more, the genotype-phenotype correlation analysis was performed bttween the gout patients.Results:①Gout cases and controls are matched by age(P>0.05), the body mass index, waist to hip ratio, systolic blood pressure, diastolic blood pressure, blood glucose, uric acid, triglycerides, blood urea nitrogen and creatinine of gout group are significantly higher than controls(P<0.05).15.45%of gout patients suffer from tophi.②There was a clear link between the gout and rs13124007, rs6850166, rs2231142 and the A allele of rs6850166 and rs2231142 appeared to be the risk allele for susceptibility to gout (p= 0.002, OR 2.31 [95%CI 1.33-4.01]; p< 0.001, OR 1.88 [95%CI 1.35-2.62]),theC allele of rs13124007 in the gout group were significantly higher than the controls(p= 0.034, OR 1.73 [95%CI 1.04-2.89]).②No significant differences of phenotype between individuals carrying the GG,GC and CC genotype in rs13124007 (P>0.05). There are more obesity risk who carrying GA and AA genotype in rs6850166 locus (P= 0.026, OR 0.21 [95%CI 0.04-0.93]; P= 0.041, OR 0.28 [95%CI 0.08-1.01]). There are greater waist-hip ratio in the individuals who carrying the AA genotype comparing CC genotype (P=0.047). Individuals who carrying the AA and CA genotype have higher systolic blood pressure (P= 0.021), uric acid concentration (P= 0.037), triglyceride levels (P= 0.038) and total cholesterol levels (P= 0.012), and comparing with CC genotype, more individuals carrying AA and CA genotype suffering hypertension and diabetes (P= 0.018, OR 0.26 [95%CI,1.17-6.08]; P= 0.041, OR 3.62 [95%CI 0.99-13.18]).Conclusion:The Polymorphisms of rs13124007(G/C), rs6850166(G?A) and rs2231142(C/A) are associated with susceptibility to gout in Chinese Han females and A allele in rs2231142 may be relate to the level of blood pressure, blood glucose and blood lipid between gout patients.更多还原