【摘要】：背景:瘢痕疙瘩通常在皮膚損傷愈合后發(fā)生,表現(xiàn)為過度增生的致密纖維組織,超過原損傷的范圍,不能自行消退,可伴有不同程度的瘙癢和疼痛,切除后易復(fù)發(fā)。所有年齡段均可出現(xiàn)瘢痕疙瘩,常見發(fā)病年齡段為15至24歲之間。瘢痕疙瘩是僅發(fā)生于人類的一種病理現(xiàn)象,目前尚未能建立病理動物模型。瘢痕疙瘩發(fā)病機(jī)制迄今不明,主要呈現(xiàn)散發(fā)發(fā)病,具有家族聚集性特征。不同膚色人種發(fā)病率具有較大變化,黑種人發(fā)病率可達(dá)16%,白種人發(fā)病率在4.5%左右,二者發(fā)病率差距可達(dá)5~15倍。有色人種的高發(fā)病率,家族聚集性特征提示瘢痕疙瘩發(fā)病與遺傳因素存在高度的相關(guān)性。前期通過家系連鎖分析技術(shù)發(fā)現(xiàn)染色體2q23、7p11、18q21.1與瘢痕疙瘩易感性相關(guān),其遺傳模式呈現(xiàn)隱性遺傳模式。Nakashima等2010年利用全基因組關(guān)聯(lián)分析技術(shù)在日本人群中發(fā)現(xiàn)了1q41、3q22.3、15p21.3與瘢痕疙瘩顯著相關(guān)聯(lián)。2013年,朱飛等在中國人群驗(yàn)證了1q41、15p21.3的易感位點(diǎn),但3q22-23易感SNP點(diǎn)(rs940187和rs1511412)驗(yàn)證失敗,未達(dá)到顯著關(guān)聯(lián)性。我們知道,不同人群存在遺傳結(jié)構(gòu)上的差異,那么,上述研究結(jié)果的不一致性,是由于遺傳結(jié)構(gòu)上的差異性?還是因?yàn)檠芯恐袠颖玖枯^小?這些日本人群和中國漢族人群的是否具有相同的瘢痕疙瘩易感位點(diǎn)?這些都有待于我們繼續(xù)進(jìn)行研究。目的:通過對臨床收集的瘢痕疙瘩患者和正常對照樣本信息的分析,進(jìn)一步探討染色體3q22-23區(qū)域遺傳變異與中國漢族人群瘢痕疙瘩是否具有易感相關(guān)性。方法:1.檢索文獻(xiàn),查找既往報(bào)道的瘢痕疙瘩易感位點(diǎn),納入研究中染色體3q22-23區(qū)域2個SNPs位點(diǎn)(rs940187、rs1511412)。通過Sequenom MassARRAY技術(shù)平臺對rs940187和rs1511412進(jìn)行基因分型。研究人群包括病例組:309個瘢痕疙瘩患者,對照組:1080個健康體檢人員,所有納入研究對象均為漢族人群�；蚍中徒Y(jié)果利用Plink 1.07軟件進(jìn)行分析,計(jì)算rs940187、rs1511412基因頻率在病例-對照間的分布,同時結(jié)果用Bonferroni方法進(jìn)一步校正。2.關(guān)于rs1511412多態(tài)性與瘢痕疙瘩關(guān)系的病例-對照研究的中英文相關(guān)文獻(xiàn)在PubMed數(shù)據(jù)庫、中國生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫及中國知網(wǎng)進(jìn)行檢索,對符合納入標(biāo)準(zhǔn)的中英文獻(xiàn)采Rev Man5.0 Meta軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:1.瘢痕疙瘩組和對照組的rs940187、rs1511412分型結(jié)果統(tǒng)計(jì)分析顯示rs940187與中國漢族瘢痕疙瘩遺傳易感性顯著相關(guān)(OR=1.88,95%CI1.27-2.78,P=1.35E-3),而rs1511412僅僅顯示與瘢痕疙瘩的遺傳有傾向性(OR=2.23,95%CI 1.09-4.55,P=2.37E-2)。2.通過Meta分析,我們發(fā)現(xiàn)rs1511412位點(diǎn)的基因型在病例組和對照組人群中分布有顯著差異,具有統(tǒng)計(jì)學(xué)意義(P1×10-8OR=1.89)。結(jié)論:1.本次研究在病例對照關(guān)聯(lián)研究的基礎(chǔ)上,發(fā)現(xiàn)位于BPESC1基因上rs940187 SNP位點(diǎn)與瘢痕疙瘩具有顯著關(guān)聯(lián)性,這個位點(diǎn)堿基的變異可能通過影響B(tài)PESC1基因編碼的蛋白,參與瘢痕疙瘩的發(fā)病。由于目前對BPESC1基因功能學(xué)的研究不足,故rs940187位點(diǎn)變異在瘢痕疙瘩發(fā)病機(jī)制中的作用還有待進(jìn)一步去研究。2.位于FOXL2基因上的rs1511412位點(diǎn)與瘢痕疙瘩具有相關(guān)性,這個位點(diǎn)堿基的變化可能通過影響類固醇激素、促性腺激素和孕期雌激素參與瘢痕疙瘩發(fā)病。綜上所述染色體3q22-23是中國漢族人群瘢痕疙瘩的易感區(qū)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.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R622

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