本文選題：白癜風(fēng) + MHC�。� 參考：《安徽醫(yī)科大學(xué)》2011年碩士論文

【摘要】：背景白癜風(fēng)(OMIM,#193200)屬于一種多基因遺傳病,因不同種族不同地域而呈現(xiàn)不同的患病率[2-4]。白癜風(fēng)是一種常見的色素減退性皮膚病,主要侵犯皮膚及毛發(fā)的發(fā)病機(jī)制不明的復(fù)雜性疾病。其發(fā)病機(jī)制迄今尚未完全闡明,目前認(rèn)為機(jī)制包括遺傳學(xué)說、自身免疫學(xué)說、黑素細(xì)胞自身破壞學(xué)說、神經(jīng)化學(xué)因子學(xué)說等,但均未定論。其中遺傳因素在白癜風(fēng)的發(fā)病中具有重要作用。以往主要通過連鎖分析和候選基因方法研究白癜風(fēng)的易感基因�，F(xiàn)在我們通過全基因組關(guān)聯(lián)分析研究發(fā)現(xiàn)在MHC區(qū)域上發(fā)現(xiàn)兩個(gè)獨(dú)立的關(guān)聯(lián)信號即突變位點(diǎn)(rs11966200, rs9468925 ),進(jìn)一步研究發(fā)現(xiàn)rs1196200可能與HLA-A*3001, HLA-B*1302, HLA-C*0602以及HLA-DRB1*0701的等位基因相關(guān)聯(lián),而rs9468925可能代表了一個(gè)以前所未知的易感基因。同時(shí)還發(fā)現(xiàn)了一個(gè)以前未被描述的風(fēng)險(xiǎn)位點(diǎn)位于6q27(rs2236313),此處包含了三個(gè)基因RNASET2, FGFR1OP和CCR6。為探討該SNP位點(diǎn)是否與漢族人白癜風(fēng)表型相關(guān),本研究應(yīng)用課題組白癜風(fēng)易感基因的GWA研究結(jié)果,分析MHC區(qū)域上的一個(gè)SNPrs9468925的單核苷酸多態(tài)性與漢族人尋常型白癜風(fēng)表型的關(guān)系。 目的對尋常型白癜風(fēng)發(fā)病年齡、發(fā)病面積、家族史、伴發(fā)自身免疫疾病及臨床類型進(jìn)行分層分析,在漢族人群中研究尋常型白癜風(fēng)MHC區(qū)域一個(gè)SNPrs9468925單核苷酸多態(tài)性與白癜風(fēng)表型的相關(guān)性,為進(jìn)一步探討白癜風(fēng)的發(fā)病機(jī)制提供重要的遺傳學(xué)依據(jù)。 方法5,566例白癜風(fēng)患者和6,462例正常對照的MHC區(qū)域單核苷酸多態(tài)性rs9468925位點(diǎn)基因分型(AA、AG、GG)資料均來源于本課題組白癜風(fēng)全基因組關(guān)聯(lián)分析的Illumina 610芯片分型數(shù)據(jù),數(shù)據(jù)資料經(jīng)適當(dāng)轉(zhuǎn)化后應(yīng)用社會科學(xué)統(tǒng)計(jì)軟件包SPSS10.0對資料進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果1.病例組與對照組的基因型總體分布差異具有統(tǒng)計(jì)學(xué)意義(χ~2=138.4,df=2,P=8.85×10~(-31)),病例組與對照組的等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=136.49,df=1,P=1.56×10~(-31),OR= 0.73,95%CI:0.69-0.77)。2.發(fā)病患者年齡≤20歲與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=140.93,df=2,P=2.50×10~(-31);χ~2=140.42,df=1,P=2.16×10~(-32),OR= 0.68,95%CI:0.63-0.72)。發(fā)病患者年齡20歲與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=43.87,df=2,P=2.97×10~(-10);χ~2=43.23,df=1,P=4.87×10~(-11),OR 0.80,95%CI 0.74-0.85)。發(fā)病患者≤20歲和發(fā)病患者20歲之間rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=16.53,df=2,P=2.57×10~(-4);χ~2=16.1,df=1,P=6.01×10~(-5),OR= 0.80,95%CI:0.74-0.85)。3.涉及皮損面積5%的患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=109.4,df=2,P=1.72×10~(-24);χ~2=109.67,df=1,P=1.16×10~(-25),OR= 0.73,95%CI:0.69-0.77)。涉及皮損面積≥5%的患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=63.79,df=2,P=1.41×10~(-14);χ~2=58.71,df=1,P=1.83×10~(-14),OR= 0.72,95%CI:0.66-0.78)。涉及皮損面積5%的患者和涉及皮損面積≥5%的患者之間rs9468925位點(diǎn)基因型有統(tǒng)計(jì)學(xué)意義(χ~2=7.39,df=2,P=0.025),等位基因分布差異無統(tǒng)計(jì)學(xué)意義(χ~2=0.3,df=1,P=0.58,OR= 1.03,95%CI:0.94-1.12)。4.家族史陽性患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=34.97,df=2,P=2.55×10~(-8);χ~2=32.92,df=1,P=9.59×10~(-9),OR= 0.70,95%CI:0.63-0.79)。家族史陰性患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=63.79,df=2,P=1.41×10~(-14);χ~2=58.71,df=1,P=1.83×10~(-14),OR= 0.72,95%CI:0.66-0.78)。家族史陽性患者和陰性患者間rs9468925位點(diǎn)基因型和等位基因分布差異均無統(tǒng)計(jì)學(xué)意義(χ~2=3.28,df=2,P=0.19;χ~2=0.38,df=1,P=0.54,OR =0.96,95%CI:0.85-1.09)。5.伴發(fā)自身免疫疾病的患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=14.23,df=2,P=0.001;χ~2=13.94,df=1,P=1.88×10~(-4),OR= 0.72,95%CI:0.60-0.85)。不伴發(fā)自身免疫疾病的患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=132.93,df=2,P=1.36×10~(-29);χ~2=131.18,df=1,P=1.93×10~(-30),OR= 0.73,95%CI:0.69-0.77)。伴發(fā)自身免疫疾病的患者和不伴發(fā)自身免疫疾病的患者之間rs9468925位點(diǎn)基因型和等位基因分布差異均無統(tǒng)計(jì)學(xué)意義(χ~2=0.43,df=2,P=0.81;χ~2=0.57,df=1,P=0.45,OR= 1.09,95%CI:0.87-1.37)。6.局限型患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異均有統(tǒng)計(jì)學(xué)意義(χ~2=38.04,df=2,P=5.48×10~(-9);χ~2=37.06,df=1,P=1.14×10~(-9),OR= 0.79,95%CI:0.73-0.85)。散發(fā)型患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=121.83,df=2,P=3.51×10~(-27);χ~2=119.87,df=1,P=6.76×10~(-28),OR= 0.70,95%CI:0.66-0.75)。泛發(fā)型患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=14.41,df=2,P=0.001;χ~2=13.31,df=1,P=2.64×10~(-4),OR= 0.79,95%CI:0.73-0.85)。面肢型患者與對照比較,rs9468925位點(diǎn)基因型和等位基因分布差異亦具有統(tǒng)計(jì)學(xué)意義(χ~2=17.00,df=2,P=2.04×10~(-4);χ~2=16.05,df=1,P=6.17×10~(-5),OR= 0.72,95%CI:0.62-0.85)。各臨床類型患者rs9468925位點(diǎn)基因型分布差異有統(tǒng)計(jì)學(xué)意義(χ~2=13.98,df=6,P=0.03),等位基因分布差異無統(tǒng)計(jì)學(xué)意義(χ~2=6.74,df=3,P=0.08)。 結(jié)論1.MHC區(qū)域rs9468925遺傳多態(tài)性與漢族人尋常型白癜風(fēng)的易感性相關(guān)。2.漢族人白癜風(fēng)患者M(jìn)HC區(qū)域rs9468925遺傳多態(tài)性與發(fā)病年齡有顯著相關(guān)性。3.漢族人白癜風(fēng)患者M(jìn)HC區(qū)域rs9468925遺傳多態(tài)性與發(fā)病面積有顯著相關(guān)。4.MHC區(qū)域rs9468925遺傳多態(tài)性與漢族人白癜風(fēng)的臨床發(fā)病類型有顯著相關(guān)性。MHC區(qū)域rs9468925遺傳多態(tài)性均對白癜風(fēng)的有無家族史,是否伴發(fā)自身免疫性疾病的影響作用較弱,可能與白癜風(fēng)具有不同的遺傳學(xué)基礎(chǔ)和不同的發(fā)病機(jī)制有關(guān)。
[Abstract]:Background OMIM (#193200) belongs to a polygenic disease. The incidence of vitiligo in different races and different regions [2-4]. is a common pigmented dermatosis, which mainly invades the complicated and complex diseases of the skin and hair. Its pathogenesis has not yet been fully elucidated, and the mechanism is now considered to be the mechanism. It includes genetic theory, autoimmune theory, melanocyte self destruction theory, neurochemical factor theory, etc. but the genetic factors play an important role in the pathogenesis of vitiligo. Past linkage analysis and candidate gene methods have been used to study the susceptibility genes of vitiligo. The study found that two independent correlation signals, rs11966200 (rs9468925), were found in the MHC region. Further studies found that rs1196200 might be associated with HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles, and rs9468925 may represent a previously unknown susceptibility gene. A previously unknown risk locus is located in 6q27 (rs2236313), which contains three genes RNASET2, FGFR1OP and CCR6. to investigate whether the SNP locus is associated with the phenotype of vitiligo in Han people. This study applies the results of the GWA study on the susceptible gene of vitiligo to analyze a single nucleotide polymorphisms on a SNPrs9468925 in MHC region. The relationship between sex and the phenotype of vitiligo vulgaris.
Objective to analyze the age, area, family history, autoimmune diseases and clinical types of vitiligo vulgaris, and to study the correlation of a single nucleotide polymorphism of SNPrs9468925 in the MHC area of vitiligo vulgaris to the phenotype of vitiligo, and to provide an important approach to further explore the pathogenesis of vitiligo. Genetic basis.
Methods the MHC regional single nucleotide polymorphic rs9468925 loci genotyping (AA, AG, GG) data from 5566 patients with vitiligo and 6462 normal controls were derived from the Illumina 610 chip data of the whole genome association analysis of vitiligo in our group. The data were properly converted to the data of the social science statistics software package and SPSS10.0 to the data. Make a statistical analysis.
Results the total distribution of genotypes between the 1. cases group and the control group was statistically significant (x ~2=138.4, df=2, P=8.85 x 10~ (-31)), and the difference of allele distribution between the case group and the control group was also statistically significant (x ~2=136.49, df=1, P=1.56 * 10~ (-31), OR= 0.73,95%CI:0.69-0.77) and the age of the patients was less than 20 years old and compared with the control. The differences in the distribution of genotypes and alleles at 25 loci were statistically significant (x ~2=140.93, df=2, P=2.50 x 10~ (-31), X ~2=140.42, df=1, P=2.16 * 10~ (-32), OR= 0.68,95%CI:0.63-0.72). The difference of genotype and allele distribution between the age 20 and the control was also statistically significant. 10~ (-10); X ~2=43.23, df=1, P=4.87 * 10~ (-11), OR 0.80,95%CI 0.74-0.85). There are significant differences in the genotype and allele distribution of the rs9468925 loci between the 20 years of age and the 20 year old patients. The differences in genotype and allele distribution of rs9468925 loci were statistically significant (x ~2=109.4, df=2, P=1.72 x 10~ (-24), X ~2=109.67, df=1, P=1.16 x 10~ (-25), OR=). Statistical significance (x ~2=63.79, df=2, P=1.41 x 10~ (-14); Chi ~2=58.71, df=1, P=1.83 * 10~ (-14), OR= 0.72,95%CI:0.66-0.78). There were statistical significance in the genotype between patients involving skin lesion area 5% and patients involving skin lesion area more than 5%. P=0.58, OR= 1.03,95%CI:0.94-1.12).4. family history positive patients compared with the control, rs9468925 locus genotype and allele distribution difference were statistically significant (x ~2=34.97, df=2, P=2.55 x 10~ (-8)). The difference of allele distribution was also statistically significant (x ~2=63.79, df=2, P=1.41 x 10~ (-14), X ~2=58.71, df=1, P=1.83 * 10~ (-14), OR= 0.72,95%CI:0.66-0.78). =0.96,95%CI:0.85-1.09) the differences in genotype and allele distribution of rs9468925 loci in.5. patients with autoimmune diseases were statistically significant (x ~2=14.23, df=2, P=0.001; Chi ~2=13.94, df=1, P=1.88 * 10~ (-4), OR=). The distribution of genotypes and alleles also had statistical significance (x ~2=132.93, df=2, P=1.36 x 10~ (-29), X ~2=131.18, df=1, P=1.93 * 10~ (-30), OR= 0.73,95%CI:0.69-0.77). There was no statistical difference between the genotype and allele distribution in patients with autoimmune diseases and patients without autoimmune disease. Significance (chi ~2=0.43, df=2, P=0.81; Chi ~2=0.57, df=1, P=0.45, OR= 1.09,95%CI:0.87-1.37).6. localized patients compared with the control, the differences in the genotype and allele distribution of the rs9468925 loci were statistically significant (x ~2=38.04, df=2). The distribution of genotypes and alleles of rs9468925 loci was also statistically significant (x ~2=121.83, df=2, P=3.51 x 10~ (-27), X ~2=119.87, df=1, P=6.76 x 10~ (-28), OR=). P=0.001; X ~2=13.31, df=1, P=2.64 x 10~ (-4), OR= 0.79,95%CI:0.73-0.85). Compared with the control, the differences in the genotype and allele distribution of the rs9468925 loci were also statistically significant (chi ~2=17.00, df=2, P=2.04 x). The distribution of genotype was statistically significant (x ~2=13.98, df=6, P=0.03), and allele distribution was not statistically significant (x ~2=6.74, df=3, P=0.08).
Conclusion the genetic polymorphism of rs9468925 in 1.MHC region is associated with susceptibility to vitiligo vulgaris in Han people. The genetic polymorphism of rs9468925 in the MHC region of patients with vitiligo in.2. Han people is significantly related to the age of onset.3., the genetic polymorphism of rs9468925 in the MHC region of the Han people with vitiligo is significantly related to the.4.MHC region rs9468925 inheritance. There is a significant correlation between polymorphism and the clinical type of vitiligo in Han people..MHC region rs9468925 genetic polymorphism has no family history of vitiligo, and it has a weak influence on autoimmune diseases. It may be related to different genetic basis and different pathogenesis of vitiligo.

【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R758.41

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;白癜風(fēng)臨床分型及療效標(biāo)準(zhǔn)(2003年修訂稿)[J];中華皮膚科雜志;2004年07期

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本文編號：1890295