白癜风黑素刺激素受体1单核苷酸多态性分析
发布时间：2019-07-09 21:02
【摘要】： 随着人类基因组计划的完成,个体遗传变异与疾病的关系日益受到重视,单核苷酸多态性(SNP)是遗传学变异最常见的一种类型,也是个体临床表型多样性的重要基础,同时开展对复杂疾病的SNP研究有利于提高对这些疾病临床上预防和治疗的水平有重要意义。 白癜风是一种临床上以片状色素脱失斑为特征的皮肤病,较为常见,多数白癜风患者不伴有系统疾病,但是其皮损的存在严重影响美容,患者治疗意愿迫切。目前认为白癜风是一种复杂疾病,其发病和多个基因相关,并受到环境等因素的影响,同时组织病理学的证据提示白癜风皮损处有局部黑素细胞的缺失或减少,所以我们认为白癜风的发病和患者的黑素细胞功能相关。黑素刺激素受体1基因(melanocortin-1 receptor,MC1R)是黑素细胞表面的特异性受体,该基因被证实和人类色素的差异已及黑素瘤等疾病的发生相关,是和黑素细胞相关的疾病的一个重要基因,所以我们推测MC1R的多态性可能和白癜风的发病相关。 为了证实以上推测,我们首先对365例寻常型白癜风患者的皮损面积、发病部位、家族史、基础疾病等临床特征进行总结,找出其临床特点和可能发病相关因素。发现其中13.15%患者有家族史,提示寻常型白癜风发病可能和遗传相关。继续对40例寻常型白癜风患者(白癜风组)和38例门诊体检正常人(对照组)的MC1R的外显子进行直接测序,并同NCBI上最新的亚洲人的MC1R的SNP检测结果(文献组)进行比较分析。 主要研究结果如下: 1.白癜风临床分析结果365例寻常型白癜风中男性193例(52.88%),女性172例(47.12%),有家族史者48例(13.15%),一级亲属二级亲属三级亲属;皮损好发部位的顺序是面部胸腹手足腔口背部腰部四肢头皮颈项臂部。皮损面积中以占体表面积的1%～5%最为多见(44.11%),男性患者就诊时面积大的皮损的比例比女性高(χ~2=16.399,0.01P0.05)。有诱发因素者82例,占22.47%,精神紧张占总数的10.68% ,精神抑郁6.30%。 2.白癜风和MC1R相关性分析结果白癜风组和对照组MC1R基因共发现5个SNP位点G274A(Val92Met )、T359C ( His120His )、G488A ( Gln163Arg )、C491A(Ala164Gln)、A942G(Thr312Thr) ,其中多态性较高的两个位点是G274A(Val92Met)和G488A(Gln163Arg);白癜风组Val92Met位点和Gln163Arg位点的多态性频率分别为26.25%和81.25%,而对照组分别为22.37%和57.89%,χ~2检验提示白癜风组与对照组Gln163Arg之间有显著差异(χ~2=9.966,P0.01);白癜风组与文献组之间Gln163Arg多态性也差异显著(χ~2=6.214,0.01P0.05);对照组与文献组之间均无显著差异。三组之间的Val92Met位点多态性无显著差异。新发现了一个变异位点C491A(Ala164Gln)。 结论:男性寻常型白癜风患者的皮损面积就诊时一般较女性的面积要大,情绪、精神变化可能会影响白癜风发病,寻常型白癜风发病可能和遗传相关。MC1R基因的Gln163Arg的变异可能与白癜风发病有关,Val92Met与白癜风发病无明显相关性。
文内图片：
图片说明：白癜风组基因组电泳（1-12为白癜风组血液基因组DNA，，M=λDNA/HindIII）
[Abstract]:With the completion of the human genome project, the relationship between the individual genetic variation and the disease is becoming more and more important, and the single nucleotide polymorphism (SNP) is one of the most common types of genetic variation, and is also an important basis for the diversity of the individual clinical phenotype. At the same time, it is of great significance to study the SNP of complex diseases to improve the clinical prevention and treatment of these diseases. Vitiligo is a kind of skin disease which is characterized by the depigmentation of the sheet-like pigment. It is more common. Most of the patients with vitiligo are not associated with the system diseases, but the presence of the skin lesions seriously affects the beauty and the patient's treatment. It is now considered that vitiligo is a complex disease, its pathogenesis is related to multiple genes, and is affected by the factors such as the environment. At the same time, the pathological evidence is presented to suggest that there are local melanocytes in the skin of vitiligo. or decreased, so we believe that the incidence of vitiligo and the work of melanocytes in the patient Melanocortin-1 receptor (MC1R) is a specific receptor on the surface of melanocytes, which is proved to be related to the occurrence of diseases such as melanoma and the like, and is a weight of the disease associated with melanocytes. To be a gene, we have speculated that the polymorphism of MC1R may be related to the development of vitiligo In order to confirm the above, we first summarize the clinical features of the skin lesions, the incidence part, the family history, the basic disease and other clinical features of 365 patients with vitiligo, and find out the clinical features and the clinical features. It was found that 13.15% of the patients had a family history, indicating the onset of vitiligo. The exon of MC1R in 40 normal vitiligo patients (vitiligo group) and 38 out-patient physical examination normal persons (control group) was directly sequenced and the SNP detection results of the latest Asian human MC1R in NCBI (literature group) continued. ) to perform a comparative analysis. The main results are as follows:1. The clinical analysis of vitiligo is as follows:1.193 cases (52.88%),172 cases (47.12%) and 48 (13.15%) with family history. %) The order of the two-level relatives of the second-level relatives of the first-level relatives; the order of the good hair parts of the skin lesions is the facial chest and abdomen hand In the area of the skin,1% ~ 5% of the body surface area was the most common (44.11%), and the proportion of the skin lesions with large area in male patients was higher than that of the female (1 ~ 2 = 16). (399, 0.01 P.05).82 cases (22.47%) with inducing factors (22.47%), and the total number of mental stress (1%) A total of 5 SNP sites G274A (Val92Met), T359C (His120His), G488A (Gln163Arg), C491A (Ala164Gln), A942G (Thr312Thr) were found in the Vitiligo and the control group MC1R gene. The two sites with higher polymorphism were G274A (Val92Me). T) and G488A (Gln163Arg); the polymorphism frequencies of the Val92Met and Gln163Arg sites in the vitiligo group were 26.25% and 81.25%, respectively, while the control group was 22.37% and 57.89%, respectively. The difference (1-2 = 9.966, P0.01), the Gn163Arg polymorphism between the vitiligo group and the literature group was also significant (P-2 = 6.214, 0.01 P0. 05) There was no significant difference between the control group and the literature group. There was no significant difference in the Val92Met site polymorphism. A change was found Heterotopic point C491A (Ala164Gln). Conclusion: The area of the skin lesions of the patients with ordinary vitiligo is generally larger than that of the female. It may be related to the pathogenesis of vitiligo and the pathogenesis of vitiligo. The mutation of the Gln163Arg of the MC1R gene may be related to the development of vitiligo.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.41
本文编号：2512447
文内图片：
图片说明：白癜风组基因组电泳（1-12为白癜风组血液基因组DNA，，M=λDNA/HindIII）
[Abstract]:With the completion of the human genome project, the relationship between the individual genetic variation and the disease is becoming more and more important, and the single nucleotide polymorphism (SNP) is one of the most common types of genetic variation, and is also an important basis for the diversity of the individual clinical phenotype. At the same time, it is of great significance to study the SNP of complex diseases to improve the clinical prevention and treatment of these diseases. Vitiligo is a kind of skin disease which is characterized by the depigmentation of the sheet-like pigment. It is more common. Most of the patients with vitiligo are not associated with the system diseases, but the presence of the skin lesions seriously affects the beauty and the patient's treatment. It is now considered that vitiligo is a complex disease, its pathogenesis is related to multiple genes, and is affected by the factors such as the environment. At the same time, the pathological evidence is presented to suggest that there are local melanocytes in the skin of vitiligo. or decreased, so we believe that the incidence of vitiligo and the work of melanocytes in the patient Melanocortin-1 receptor (MC1R) is a specific receptor on the surface of melanocytes, which is proved to be related to the occurrence of diseases such as melanoma and the like, and is a weight of the disease associated with melanocytes. To be a gene, we have speculated that the polymorphism of MC1R may be related to the development of vitiligo In order to confirm the above, we first summarize the clinical features of the skin lesions, the incidence part, the family history, the basic disease and other clinical features of 365 patients with vitiligo, and find out the clinical features and the clinical features. It was found that 13.15% of the patients had a family history, indicating the onset of vitiligo. The exon of MC1R in 40 normal vitiligo patients (vitiligo group) and 38 out-patient physical examination normal persons (control group) was directly sequenced and the SNP detection results of the latest Asian human MC1R in NCBI (literature group) continued. ) to perform a comparative analysis. The main results are as follows:1. The clinical analysis of vitiligo is as follows:1.193 cases (52.88%),172 cases (47.12%) and 48 (13.15%) with family history. %) The order of the two-level relatives of the second-level relatives of the first-level relatives; the order of the good hair parts of the skin lesions is the facial chest and abdomen hand In the area of the skin,1% ~ 5% of the body surface area was the most common (44.11%), and the proportion of the skin lesions with large area in male patients was higher than that of the female (1 ~ 2 = 16). (399, 0.01 P.05).82 cases (22.47%) with inducing factors (22.47%), and the total number of mental stress (1%) A total of 5 SNP sites G274A (Val92Met), T359C (His120His), G488A (Gln163Arg), C491A (Ala164Gln), A942G (Thr312Thr) were found in the Vitiligo and the control group MC1R gene. The two sites with higher polymorphism were G274A (Val92Me). T) and G488A (Gln163Arg); the polymorphism frequencies of the Val92Met and Gln163Arg sites in the vitiligo group were 26.25% and 81.25%, respectively, while the control group was 22.37% and 57.89%, respectively. The difference (1-2 = 9.966, P0.01), the Gn163Arg polymorphism between the vitiligo group and the literature group was also significant (P-2 = 6.214, 0.01 P0. 05) There was no significant difference between the control group and the literature group. There was no significant difference in the Val92Met site polymorphism. A change was found Heterotopic point C491A (Ala164Gln). Conclusion: The area of the skin lesions of the patients with ordinary vitiligo is generally larger than that of the female. It may be related to the pathogenesis of vitiligo and the pathogenesis of vitiligo. The mutation of the Gln163Arg of the MC1R gene may be related to the development of vitiligo.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.41
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