染色体3q22-23遗传变异与中国汉族人群瘢痕疙瘩相关性研究

发布时间：2018-08-27 15:18

【摘要】：背景:瘢痕疙瘩通常在皮肤损伤愈合后发生,表现为过度增生的致密纤维组织,超过原损伤的范围,不能自行消退,可伴有不同程度的瘙痒和疼痛,切除后易复发。所有年龄段均可出现瘢痕疙瘩,常见发病年龄段为15至24岁之间。瘢痕疙瘩是仅发生于人类的一种病理现象,目前尚未能建立病理动物模型。瘢痕疙瘩发病机制迄今不明,主要呈现散发发病,具有家族聚集性特征。不同肤色人种发病率具有较大变化,黑种人发病率可达16%,白种人发病率在4.5%左右,二者发病率差距可达5~15倍。有色人种的高发病率,家族聚集性特征提示瘢痕疙瘩发病与遗传因素存在高度的相关性。前期通过家系连锁分析技术发现染色体2q23、7p11、18q21.1与瘢痕疙瘩易感性相关,其遗传模式呈现隐性遗传模式。Nakashima等2010年利用全基因组关联分析技术在日本人群中发现了1q41、3q22.3、15p21.3与瘢痕疙瘩显著相关联。2013年,朱飞等在中国人群验证了1q41、15p21.3的易感位点,但3q22-23易感SNP点(rs940187和rs1511412)验证失败,未达到显著关联性。我们知道,不同人群存在遗传结构上的差异,那么,上述研究结果的不一致性,是由于遗传结构上的差异性?还是因为研究中样本量较小?这些日本人群和中国汉族人群的是否具有相同的瘢痕疙瘩易感位点?这些都有待于我们继续进行研究。目的:通过对临床收集的瘢痕疙瘩患者和正常对照样本信息的分析,进一步探讨染色体3q22-23区域遗传变异与中国汉族人群瘢痕疙瘩是否具有易感相关性。方法:1.检索文献,查找既往报道的瘢痕疙瘩易感位点,纳入研究中染色体3q22-23区域2个SNPs位点(rs940187、rs1511412)。通过Sequenom MassARRAY技术平台对rs940187和rs1511412进行基因分型。研究人群包括病例组:309个瘢痕疙瘩患者,对照组:1080个健康体检人员,所有纳入研究对象均为汉族人群。基因分型结果利用Plink 1.07软件进行分析,计算rs940187、rs1511412基因频率在病例-对照间的分布,同时结果用Bonferroni方法进一步校正。2.关于rs1511412多态性与瘢痕疙瘩关系的病例-对照研究的中英文相关文献在PubMed数据库、中国生物医学文献数据库及中国知网进行检索,对符合纳入标准的中英文献采Rev Man5.0 Meta软件进行统计学分析。结果:1.瘢痕疙瘩组和对照组的rs940187、rs1511412分型结果统计分析显示rs940187与中国汉族瘢痕疙瘩遗传易感性显著相关(OR=1.88,95%CI1.27-2.78,P=1.35E-3),而rs1511412仅仅显示与瘢痕疙瘩的遗传有倾向性(OR=2.23,95%CI 1.09-4.55,P=2.37E-2)。2.通过Meta分析,我们发现rs1511412位点的基因型在病例组和对照组人群中分布有显著差异,具有统计学意义(P1×10-8OR=1.89)。结论:1.本次研究在病例对照关联研究的基础上,发现位于BPESC1基因上rs940187 SNP位点与瘢痕疙瘩具有显著关联性,这个位点碱基的变异可能通过影响BPESC1基因编码的蛋白,参与瘢痕疙瘩的发病。由于目前对BPESC1基因功能学的研究不足,故rs940187位点变异在瘢痕疙瘩发病机制中的作用还有待进一步去研究。2.位于FOXL2基因上的rs1511412位点与瘢痕疙瘩具有相关性,这个位点碱基的变化可能通过影响类固醇激素、促性腺激素和孕期雌激素参与瘢痕疙瘩发病。综上所述染色体3q22-23是中国汉族人群瘢痕疙瘩的易感区域。
[Abstract]:BACKGROUND: Keloids usually occur after the healing of skin lesions, which are characterized by excessive hyperplasia of dense fibrous tissue beyond the scope of the original injury and can not subside spontaneously. They can be accompanied by varying degrees of itching and pain, and are prone to recurrence after excision. The pathogenesis of keloid is still unknown, mainly sporadic and family aggregation. The incidence of keloid varies greatly in different skin color races. The incidence of black and white people can reach 16% and 4.5% respectively. High incidence of colored people and familial aggregation suggest a high degree of correlation between keloid and genetic factors. Previous studies revealed that chromosomes 2q23, 7p11, 18q21.1 were associated with keloid susceptibility through family linkage analysis, and the genetic model presented a recessive genetic model. Nakashima et al. used the whole genome in 2010. In 2013, Zhu Fei et al. verified the susceptibility loci of 1q41, 15p21.3 in Chinese population, but the susceptibility SNP loci of 3q22-23 (rs940187 and rs1511412) failed to validate the association. We know that different populations have genetic structure. So, the inconsistency of the above results is due to genetic differences or small sample size? Do these Japanese and Chinese Han people have the same keloid susceptibility loci? These are still to be studied. Methods: 1. Retrieving the literatures and searching for the previously reported susceptibility sites of keloid, two SNPs (rs0187, rs15112) in chromosome 3q22-23 region were included in the study. Sequenom Mass ARRAY was used to genotype rs940187 and rs1511412. The study population included 309 keloid patients and 1080 healthy persons. The genotyping results were analyzed by Plink 1.07 software, and the rs940187 and rs1511412 gene frequencies were calculated. The case-control study on the relationship between rs1511412 polymorphism and keloid was retrieved in PubMed database, China Biomedical Literature Database and China HowNet. The Chinese and English literatures that met the inclusion criteria were collected by Rev Man 5.0 Meta. Results: 1. The results of rs940187 and rs1511412 typing in keloid group and control group showed that rs940187 was significantly associated with the genetic susceptibility of keloid in Chinese Han nationality (OR = 1.88, 95% CI 1.27-2.78, P = 1.35E-3), whereas rs15112 only showed a genetic predisposition to keloid (OR = 2.23, 95% CI 1.55, P = 4.55). 2.37E-2). 2. By meta-analysis, we found that the genotype of rs1511412 locus was significantly different between the case group and the control group (P1 *10-8OR=1.89). Conclusion: 1. Based on the case-control study, we found that rs0187 SNP locus on BPESC1 gene was significantly associated with keloid. Linkage, the mutation of this site base may be involved in the pathogenesis of keloid by affecting the protein encoded by BPESC1 gene. Due to insufficient research on the function of BPESC1 gene, the role of rs940187 mutation in the pathogenesis of keloid remains to be further studied. There is a correlation between keloids. The change of the base at this locus may be involved in the pathogenesis of keloids by affecting steroids, gonadotrophins and estrogens during pregnancy.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R622

【参考文献】