骨保护素基因多态性与多发性骨髓瘤骨病相关性研究

发布时间：2018-01-17 20:03

本文关键词：骨保护素基因多态性与多发性骨髓瘤骨病相关性研究　出处：《福建医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:探讨骨保护素(Osteoprotegerin,OPG)基因A163G、T245G、C950T及C1181G位点基因多态性、单体型分布及血清OPG浓度与多发性骨髓瘤骨病(myeloma bone disease,MBD)的关系。方法:采用病例-对照的设计方法,用DNA直接测序法检测48例骨髓瘤患者(其中骨髓瘤伴骨病患者40例)和50例健康对照者OPG基因A163G、T245G、C950T及C1181G位点的多态性及用ELISA法检测血清OPG浓度,运用SHEsis在线生物信息学软件对以上位点的基因型、等位基因、连锁不平衡(LD)、单体型分布特征进行分析。同时收集MM患者起病年龄、性别、吸烟史、ISS分期、β2微球蛋白等临床资料,运用SPSS 17统计学软件进行基因型与临床资料相关性分析。结果:1、对照组各位点均符合Hardy-Weinberg遗传平衡,950位点T等位基因在MBD组(71.1%)显著高于对照组(56%),差异有统计学意义(c2=4.175,P=0.041),提示为MBD的高风险性等位基因;1181位点G等位基因频率分布在MBD组(81.6%)高于对照组(67%),差异有统计学意义(c2=4.689,P=0.030),提示为MBD的高风险性等位基因。未发现4个位点的基因型和A163G、T245G的等位基因与MBD患病风险相关。2、分析MBD组4个位点基因型与临床指标的相关性,发现950CT及1181GG在女性患者中分布较多,差异有统计学意义(P0.05),C950T、C1181G与性别具有相关性。未发现这两个位点与其它临床指标有相关性。A163G、T245G位点与所收集的临床指标均无相关性。3、分析遗传标记两两之间连锁不平衡,发现4个位点中A163G-T245G之间存在连锁不平衡(LD),但未发现A163G-T245G组成的单体型与MBD易感性相关。163-245-950-1181组成的9种可能的单体型,A T T G是病例组和对照组中最常见的单体型;A T C C单体型在病例组的频率(14.1%)明显低于对照组(26.9%),组间比较差异有统计学意义(P=0.031,OR 0.426,(95%CI)0.194~0.936),提示此单体型可降低MBD发病风险,为MBD的保护性单体型;G G T G单体型在病例组的频率(8.8%)高于对照组(0%),组间比较差异有统计学意义(p=0.003)提示此单体型可增加MBD发病风险,为MBD的易感单体型。4、MBD组血清OPG浓度低于正常组,组间比较差异有统计学意义(p0.05)。结论:1、950T、1181G等位基因及A T C C单体型、G G T G单体型在骨髓瘤骨病的发生发展过程具有重要作用。OPG基因多态性可作为评估MBD患病风险潜在的分子标记。2、血清OPG浓度降低可能是骨髓瘤骨病的危险因素。
[Abstract]:Objective: to investigate the polymorphism of Osteoprotegerin Osteoprotegerin OPG (Osteoprotegerin Osteoprotegerin Osteoprotegerin OPG) gene at C950T and C1181G loci. Relationship between haplotype distribution and serum OPG concentration in patients with multiple myeloma bone disease. Methods: a case-control design was used. OPG gene A163G T245G was detected by direct DNA sequencing in 48 myeloma patients (40 myeloma patients with bone disease) and 50 healthy controls. The polymorphism of C950T and C1181G loci and the concentration of serum OPG were detected by ELISA method. The genotypes and alleles of the above loci were detected by SHEsis online bioinformatics software. At the same time, the age, sex, smoking history and ISS stage, 尾 2 microglobulin and other clinical data of MM patients were collected. SPSS 17 statistical software was used to analyze the correlation between genotype and clinical data. Results: 1. All the points in the control group were in accordance with the Hardy-Weinberg genetic balance. The T allele at 950locus in MBD group was significantly higher than that in control group (P < 0. 041). It is suggested that MBD is a high risk allele. The frequency of G allele at 1181 locus in MBD group (81.6) was higher than that in control group (P < 0.05). No allele of 4 loci and allele A163G / T245G was found to be associated with the risk of MBD. By analyzing the correlation between the four loci genotypes and clinical indexes in MBD group, it was found that 950CT and 1181GG were more distributed in female patients, and the difference was statistically significant (P0.05C950T). C1181G was correlated with sex. There was no correlation between the two loci and other clinical indexes. There was no correlation between C1181G locus and other clinical indexes. There was no correlation between C1181G locus and other clinical indexes. The linkage disequilibrium between two genetic markers was analyzed and the linkage disequilibrium between A163G-T245G was found in the four loci. But the haplotype of A163G-T245G was not found to be related to the susceptibility of MBD. There were nine possible haplotypes in A163G-T245G and the susceptibility of A163-245-950-1181. ATT T G was the most common haplotype in case group and control group. The frequency of ATC haplotype in the case group was significantly lower than that in the control group (P < 0.031 or 0.426). This haplotype can reduce the risk of MBD and be the protective haplotype of MBD. The frequency of G G T G haplotype in the case group was 8. 8% higher than that in the control group. The results showed that the haplotype increased the risk of MBD, and the serum OPG concentration in the susceptible haplotype of MBD group was lower than that in the normal group. There was significant difference between the two groups (P 0.05). Conclusion the allele of 1: 950Tnn 1181G and the A T C haplotype were significantly different between the two groups. G G T G haplotype plays an important role in the occurrence and development of myeloma osteopathy. OPG gene polymorphism can be used as a potential molecular marker for evaluating the risk of MBD. The decrease of serum OPG level may be a risk factor for myeloma osteopathy.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.3

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