【摘要】： 隨著人類基因組計(jì)劃的完成,個(gè)體遺傳變異與疾病的關(guān)系日益受到重視,單核苷酸多態(tài)性(SNP)是遺傳學(xué)變異最常見的一種類型,也是個(gè)體臨床表型多樣性的重要基礎(chǔ),同時(shí)開展對復(fù)雜疾病的SNP研究有利于提高對這些疾病臨床上預(yù)防和治療的水平有重要意義。 白癜風(fēng)是一種臨床上以片狀色素脫失斑為特征的皮膚病,較為常見,多數(shù)白癜風(fēng)患者不伴有系統(tǒng)疾病,但是其皮損的存在嚴(yán)重影響美容,患者治療意愿迫切。目前認(rèn)為白癜風(fēng)是一種復(fù)雜疾病,其發(fā)病和多個(gè)基因相關(guān),并受到環(huán)境等因素的影響,同時(shí)組織病理學(xué)的證據(jù)提示白癜風(fēng)皮損處有局部黑素細(xì)胞的缺失或減少,所以我們認(rèn)為白癜風(fēng)的發(fā)病和患者的黑素細(xì)胞功能相關(guān)。黑素刺激素受體1基因(melanocortin-1 receptor,MC1R)是黑素細(xì)胞表面的特異性受體,該基因被證實(shí)和人類色素的差異已及黑素瘤等疾病的發(fā)生相關(guān),是和黑素細(xì)胞相關(guān)的疾病的一個(gè)重要基因,所以我們推測MC1R的多態(tài)性可能和白癜風(fēng)的發(fā)病相關(guān)。 為了證實(shí)以上推測,我們首先對365例尋常型白癜風(fēng)患者的皮損面積、發(fā)病部位、家族史、基礎(chǔ)疾病等臨床特征進(jìn)行總結(jié),找出其臨床特點(diǎn)和可能發(fā)病相關(guān)因素。發(fā)現(xiàn)其中13.15%患者有家族史,提示尋常型白癜風(fēng)發(fā)病可能和遺傳相關(guān)。繼續(xù)對40例尋常型白癜風(fēng)患者(白癜風(fēng)組)和38例門診體檢正常人(對照組)的MC1R的外顯子進(jìn)行直接測序,并同NCBI上最新的亞洲人的MC1R的SNP檢測結(jié)果(文獻(xiàn)組)進(jìn)行比較分析。 主要研究結(jié)果如下: 1.白癜風(fēng)臨床分析結(jié)果365例尋常型白癜風(fēng)中男性193例(52.88%),女性172例(47.12%),有家族史者48例(13.15%),一級親屬二級親屬三級親屬;皮損好發(fā)部位的順序是面部胸腹手足腔口背部腰部四肢頭皮頸項(xiàng)臂部。皮損面積中以占體表面積的1%～5%最為多見(44.11%),男性患者就診時(shí)面積大的皮損的比例比女性高(χ~2=16.399,0.01P0.05)。有誘發(fā)因素者82例,占22.47%,精神緊張占總數(shù)的10.68% ,精神抑郁6.30%。 2.白癜風(fēng)和MC1R相關(guān)性分析結(jié)果白癜風(fēng)組和對照組MC1R基因共發(fā)現(xiàn)5個(gè)SNP位點(diǎn)G274A(Val92Met )、T359C ( His120His )、G488A ( Gln163Arg )、C491A(Ala164Gln)、A942G(Thr312Thr) ,其中多態(tài)性較高的兩個(gè)位點(diǎn)是G274A(Val92Met)和G488A(Gln163Arg);白癜風(fēng)組Val92Met位點(diǎn)和Gln163Arg位點(diǎn)的多態(tài)性頻率分別為26.25%和81.25%,而對照組分別為22.37%和57.89%,χ~2檢驗(yàn)提示白癜風(fēng)組與對照組Gln163Arg之間有顯著差異(χ~2=9.966,P0.01);白癜風(fēng)組與文獻(xiàn)組之間Gln163Arg多態(tài)性也差異顯著(χ~2=6.214,0.01P0.05);對照組與文獻(xiàn)組之間均無顯著差異。三組之間的Val92Met位點(diǎn)多態(tài)性無顯著差異。新發(fā)現(xiàn)了一個(gè)變異位點(diǎn)C491A(Ala164Gln)。 結(jié)論:男性尋常型白癜風(fēng)患者的皮損面積就診時(shí)一般較女性的面積要大,情緒、精神變化可能會影響白癜風(fēng)發(fā)病,尋常型白癜風(fēng)發(fā)病可能和遺傳相關(guān)。MC1R基因的Gln163Arg的變異可能與白癜風(fēng)發(fā)病有關(guān),Val92Met與白癜風(fēng)發(fā)病無明顯相關(guān)性。
文內(nèi)圖片：
圖片說明：白癜風(fēng)組基因組電泳（1-12為白癜風(fēng)組血液基因組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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R758.41

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