關(guān)節(jié)病型銀屑病臨床與實驗研究
發(fā)布時間：2018-07-20 13:20
【摘要】：第一部分關(guān)節(jié)病型銀屑病流行病學和臨床特征的研究 第一章關(guān)節(jié)病型銀屑病在銀屑病中構(gòu)成比及臨床特征研究 背景國外研究顯示關(guān)節(jié)病型銀屑病(PsA ,psoriatic arthritis)約占銀屑病患者的6-48%不等。而我國1984年全國銀屑病流行病調(diào)查顯示PsA在銀屑病中僅占0.69%。 目的對PsA在銀屑病中的構(gòu)成比(患病率)及其臨床特征進行研究。 方法在皮膚科門診開展一項橫斷面研究,對成年銀屑病患者的PsA患病情況進行篩查,并對臨床資料進行登記。研究方法結(jié)合關(guān)節(jié)情況問卷、體格檢查、影像學檢查以及風濕科會診的方法,采用CASPAR標準診斷。登記內(nèi)容包括性別、年齡、銀屑病發(fā)病年齡、發(fā)病時間、皮損類型、病情及嚴重程度、發(fā)病部位、銀屑病家族史,以及受累關(guān)節(jié)的發(fā)病時間、發(fā)病情況和體格檢查、輔助檢查結(jié)果等。 結(jié)果共有1928例患者參加本項研究,其中256例(13.3%)具有關(guān)節(jié)癥狀的患者進行了相應(yīng)的體格檢查和X線、CT、高頻超聲等輔助檢查。對于160例有關(guān)節(jié)癥狀而既往未經(jīng)風濕科醫(yī)生診斷的患者,請風濕科會診,以排除其他關(guān)節(jié)病變。根據(jù)CASPAR診斷標準,共確認112例PsA患者,占所有銀屑病患者的5.8%,其中103例患者(92%)為首次診斷。PsA患者中87例(77.7%)伴炎癥性外周關(guān)節(jié)炎,30例(26.8%)患者伴脊柱受累, 30例(26.8%)患者伴有附著點炎。12例(10.7%)患者外周關(guān)節(jié)和脊柱關(guān)節(jié)均受累。PsA相對特征性的遠端指間關(guān)節(jié)炎和指/趾炎,分別在27例(24.1%)和15例(13.4%)患者中出現(xiàn)。PsA患者和非PsA的銀屑病患者兩組比較顯示,PsA患者年齡稍大( 44.9 vs.35.5 years ),其皮損發(fā)病年齡略晚(30.8 vs. 27.7歲),伴晚發(fā)型銀屑病(皮損晚于40歲出現(xiàn))比例略高于非PsA患者(23.2% vs.15.6%)。PsA患者的銀屑病病程較非PsA患者長(14.1 vs 7.8年),PASI評分(9.68 vs. 6.01)和伴有紅皮病型皮損的比例(4.5% vs. 0.9%)均高于非PsA患者,且伴指甲損害(46.4% vs. 21.0%)和頭皮損害的比例亦高于非PsA患者(90.2% vs. 76.4%)。 結(jié)論PsA占銀屑病患者的5.8%,在銀屑病患者中并非少見,且多數(shù)患者處于漏診狀態(tài)。廣大皮膚科醫(yī)生應(yīng)提高對該病的重視和認識程度,以及時準確診斷和治療患者,預(yù)防畸殘的發(fā)生。 第二章關(guān)節(jié)病型銀屑病少見臨床類型的研究 第一節(jié)SAPHO綜合征22例臨床分析 背景SAPHO綜合征即滑膜炎、痤瘡、膿皰病、骨肥厚、骨炎綜合征。該病的范疇和PsA存在交叉。 目的對該病的臨床特點進行研究。 方法對22例SAPHO綜合征患者的臨床資料進行登記并分析。 結(jié)果本組病例男7例,女15例,皮損出現(xiàn)平均年齡45歲,骨關(guān)節(jié)受累平均年齡44歲。皮損表現(xiàn)為掌跖膿皰病者21例,暴發(fā)性痤瘡者1例。骨關(guān)節(jié)受累中前胸壁受累19例,外周關(guān)節(jié)者4例,骶髂關(guān)節(jié)受累2例。其中10例患者關(guān)節(jié)受累早于皮損發(fā)生,9例患者皮損早于關(guān)節(jié)受累,3例患者皮損與關(guān)節(jié)受累同時出現(xiàn)。關(guān)節(jié)受累與皮損出現(xiàn)平均間隔2.7年,最長達20年。 結(jié)論皮膚科就診的SAPHO綜合征患者以中年、女性多見。掌跖膿皰病和前胸壁骨關(guān)節(jié)受累是最常見的臨床表現(xiàn)。 第二節(jié)遠端指間關(guān)節(jié)炎型關(guān)節(jié)病型銀屑病14例分析 背景遠端指間關(guān)節(jié)炎型(distal interphalangeal predominant, DIP)PsA在臨床上相對少見。 目的對DIP型PsA的臨床特點進行研究。 方法對門診PsA患者的臨床資料進行登記,對首發(fā)類型為DIP型的14例PsA患者的臨床資料進行分析。 結(jié)果本組病例平均發(fā)病年齡41歲(23~59歲),男:女為4:3。所有患者皮損均早于關(guān)節(jié)炎發(fā)生,平均發(fā)病間隔為13年。所有患者頭皮均受累,受累關(guān)節(jié)指/趾伴甲損害者10例(71.4%)。隨著病程的進展,14例中有8例患者出現(xiàn)DIP關(guān)節(jié)外的其他關(guān)節(jié)受累,臨床分型亦出現(xiàn)變化。10例患者曾被誤診,延遲診斷時間平均為6年。 結(jié)論皮損早發(fā)于關(guān)節(jié)炎、頭皮損害及甲受累與DIP型PsA密切相關(guān)。PsA臨床分型隨著時間的變化而變化, Moll和Wright臨床分型的意義有待于進一步研究。該病臨床誤診和延遲診斷現(xiàn)象嚴重,廣大醫(yī)生需提高對該病的認識。 第二部分關(guān)節(jié)病型銀屑病易感基因研究 第一章以銀屑病GWAS結(jié)果為基礎(chǔ)的關(guān)節(jié)病型銀屑病易感基因研究 背景PsA易感基因尚未明確。近期銀屑病GWAS成功發(fā)現(xiàn)多個銀屑病易感基因位點,其中多數(shù)位點與PsA的關(guān)系尚不明了。 目的對GWAS研究發(fā)現(xiàn)的銀屑病易感基因位點在PsA、不伴有關(guān)節(jié)炎的銀屑病(PsC,psoriasis cutaneous only)及對照樣本中進行關(guān)聯(lián)研究。 方法對30個區(qū)域46個SNP,以379例PsA、595例PsC及1181例對照為樣本,以Sequenom為平臺進行基因分型,并采用Cochran-Armitage趨勢檢驗的方法進行關(guān)聯(lián)分析。采用Cochran's Q和I~2方法對PsA和PsC之間、以及脊柱型PsA和外周關(guān)節(jié)型PsA之間的異質(zhì)性進行分析。 結(jié)果本研究發(fā)現(xiàn)ERAP1基因( rs151823, p =2.82×10~(-6), OR=1.47)、IL28RA基因(rs4649203, p =6.14×10~(-6), OR=0.66)、GJB2基因(rs3751385, p= 6.59×10~(-4), OR=1.33)與PsA相關(guān),并在中國人群PsA樣本再次證實了TNIP1基因(rs17728338, p=1.84E×10~(-8) OR=1.98)和IL12B基因(rs2546890,p =4.20×10~(-7) ,OR=1.52)與PsA的相關(guān)性。亦在PTTG1、IL1、NOS2、IL23A等基因位點發(fā)現(xiàn)PsA的提示關(guān)聯(lián)信號(p0.05)。再次證實了IL28RA基因(rs4649203,p= 2.64×10~(-6) ,OR= 0.70)、ERAP1基因(rs151823, p=2.72×10~(-6),OR=1.39)、TNIP1基因(rs=17728338 p=5.29×10~(-5) , OR=1.59)、IL12B基因(rs2546890, p= 5.21E×10~(-4) ,OR=1.28)與PsC的相關(guān)性。異質(zhì)性分析發(fā)現(xiàn)PsA和PsC在ZNF816A基因(Q檢驗P值為0.04,I2 =75.97%)存在異質(zhì)性。 結(jié)論ERAP1、IL28RA、GJB2、TNIP1、IL12B等基因是PsA和PsC共有的易感基因。ZNF816A基因可能是PsC特有的易感基因,與PsA無關(guān)。 第二章以強直性脊柱炎、類風濕性關(guān)節(jié)炎GWAS結(jié)果為基礎(chǔ)的關(guān)節(jié)病型銀屑病易感基因研究 背景PsA與強直性脊柱炎、類風濕性關(guān)節(jié)炎在臨床表現(xiàn)、組織病理等方面具有某些共性,且以往研究證實這些疾病易感基因間存在交叉。 目的對近期GWAS研究發(fā)現(xiàn)的類風濕性關(guān)節(jié)炎、強直性脊柱炎易感基因SNP位點在PsA、PsC及對照樣本進行基因分型和關(guān)聯(lián)研究。 方法共選擇29個區(qū)域的36個SNP,在379例PsA、595例PsC及806例健康對照樣本中進行基因分型,并采用Cochran-Armitage趨勢檢驗的方法進行關(guān)聯(lián)分析。采用Cochran's Q和I2檢驗的方法對PsA和PsC、以及脊柱型PsA和外周關(guān)節(jié)型PsA之間的異質(zhì)性進行分析。 結(jié)果強直性脊柱炎易感基因ERAP1(rs27037,p=6.66×10~(-5),OR=1.43)和易感區(qū)域21q22.2(rs rs2242944,P=1.07×10~(-3), OR=0.72)與PsA顯著相關(guān)。強直性脊柱炎的易感基因IL23R(rs1004819,p=4.58×10~(-3),OR=1.28 )、2p15區(qū)域( rs10865331 , p=7.00×10~(-3) , OR=1.28 )及類風濕性關(guān)節(jié)炎的易感基因KIF5A-PIP4K2C(rs1678542,p=3.66×10~(-2),OR=0.81)與PsA具有提示關(guān)聯(lián)信號。ERAP1基因與PsC亦顯著相關(guān)。21q22.2區(qū)域、IL23R基因與PsC無相關(guān)性。PsA亞型分析顯示強直性脊柱炎的易感基因IL23R(rs11209032)與脊柱型PsA相關(guān)(p=1.57×10~(-3),OR= 1.52),而在僅伴有外周關(guān)節(jié)炎PsA中無陽性意義(p=5.53×10~(-1),OR=1.07)。而類風濕性關(guān)節(jié)炎易感基因AFF3、KIF5A-PIP4K2C、7q32.3區(qū)域與外周關(guān)節(jié)型PsA組存在提示關(guān)聯(lián)信號,與脊柱組無相關(guān)性。 結(jié)論ERAP1基因是PsA、PsC和強直性脊柱炎共有易感基因。21q22.2區(qū)域是PsA和強直性脊柱炎共有易感位點。脊柱型PsA與強直性脊柱炎可能具有某些共同的遺傳學背景,而外周關(guān)節(jié)型PsA則與類風濕性關(guān)節(jié)炎可能具有共同的遺傳學背景。
[Abstract]:Part one epidemiological and clinical characteristics of psoriasis arthropathy
Chapter one: the constituent ratio and clinical characteristics of psoriasis arthropathy in psoriasis
Background foreign studies have shown that PsA (psoriatic arthritis) accounts for approximately 6-48% in patients with psoriasis. In China, the National Psoriasis epidemiological survey in 1984 showed that PsA accounted for only 0.69%. in psoriasis.
Objective to study the constituent ratio (prevalence) and clinical characteristics of PsA in psoriasis.
Methods a cross-sectional study was carried out in the Department of dermatology in the Department of dermatology to screen the prevalence of PsA in adult patients with psoriasis, and to register the clinical data. The research methods were combined with the joint situation questionnaire, physical examination, imaging examination, and the methods of consultation in the Department of rheumatism, and were diagnosed by the standard of CASPAR. The registration contents include sex, age, and silver chip. Age, time of disease, type of skin lesion, condition and severity, location of the disease, family history of psoriasis, time of onset of involvement of joints, morbidity and physical examination, auxiliary examination results, etc.
Results a total of 1928 patients were enrolled in this study, of which 256 (13.3%) patients with joint symptoms were examined with corresponding physical examination and X-ray, CT, and high frequency ultrasound. For 160 patients with joint symptoms but not previously diagnosed by a department of rheumatism doctor, the Department of rheumatism consultation was requested to exclude other joint lesions. According to the diagnosis of CASPAR A total of 112 patients with PsA were identified, accounting for 5.8% of all psoriasis patients, of which 103 patients (92%) were first diagnosed with.PsA with inflammatory peripheral arthritis, 30 (26.8%) with spinal involvement, 30 (26.8%) patients (26.8%) with attachment point inflammation (10.7%), the peripheral joints and spinal joints were involved in.PsA relative characteristics. Sexual distal interphalangeal arthritis and finger / phalanges were compared in 27 (24.1%) and 15 (13.4%) patients with.PsA and non PsA psoriasis. The age of PsA patients was slightly older (44.9 vs.35.5 years). The age of the lesions was slightly late (30.8 vs. 27.7 years old), and the proportion of late psoriasis (late at 40 years old) was slightly higher than that of the late type of psoriasis. The course of psoriasis in non PsA patients (23.2% vs.15.6%) was longer than that of non PsA patients (14.1 vs 7.8 years), the PASI score (9.68 vs. 6.01) and the proportion of skin lesions with erythroderma (4.5% vs. 0.9%) were higher than those in non PsA patients, and the proportion of nail damage (46.4% vs. 21%) and head skin damage was also higher than that of non PsA patients (90.2% vs. 76.4%).
Conclusion PsA is 5.8% of psoriasis patients. It is not rare in psoriasis patients and most of the patients are in a missed diagnosis. Doctors in the General Department of Dermatology should improve the importance and understanding of the disease, and diagnose and treat patients accurately and prevent the occurrence of malformation.
The second chapter is a rare clinical type of psoriasis arthropathy.
Clinical analysis of 22 cases of SAPHO syndrome in the first section
Background SAPHO syndrome is synovitis, acne, impetigo, osteosarc and osteitis syndrome. There is a cross between PsA and the disease.
Objective to study the clinical characteristics of the disease.
Methods the clinical data of 22 patients with SAPHO syndrome were registered and analyzed.
Results there were 7 males and 15 females. The average age of skin lesions was 45 years old and the average age of bone and joint involvement was 44 years. There were 21 cases of palmar and plantar pustular disease and 1 cases of fulminant acne. 19 cases of anterior chest wall involvement in bone joint involvement, 4 cases of peripheral joint and 2 cases of sacroiliac joint involvement in the joint involvement, 10 cases of joint involvement earlier than skin lesions, 9 cases. The lesions were earlier than the joint involvement. The lesions and joint involvement occurred in 3 patients. The average interval between joint involvement and skin lesions was 2.7 years, the longest being 20 years.
Conclusion SAPHO syndrome in Department of dermatology is more common in middle-aged women than in women. Palmoplantar impetigo and anterior chest wall bone and joint involvement are the most common clinical manifestations.
Analysis of 14 cases of second cases of distal interphalangeal arthritis type psoriasis
Background distal interphalangeal predominant (DIP) PsA is relatively rare in clinic.
Objective to study the clinical characteristics of DIP type PsA.
Methods the clinical data of outpatients with PsA were registered, and the clinical data of 14 PsA patients with the initial type DIP were analyzed.
Results the average age of onset was 41 years (23~59 years), male: female: all patients with 4:3. were earlier than arthritis, with an average interval of 13 years. All the patients were involved in the scalp, and 10 cases (71.4%) were involved in the joint finger / toe with nail damage. With the progress of the disease, 8 patients in the 14 cases were affected by other joints outside the DIP joint. There was also a change in the type of bed..10 patients were misdiagnosed, and the average time to delay diagnosis was 6 years.
Conclusion the lesion of skin lesions early in arthritis, scalp damage and DIP type PsA closely related to.PsA clinical classification changes with time, the significance of clinical classification of Moll and Wright needs further study. The clinical misdiagnosis and delayed diagnosis of the disease are serious, the general doctors need to improve the understanding of the disease.
The second part is the susceptibility gene of psoriasis arthropathy.
Chapter one is based on psoriasis GWAS findings and the susceptibility genes of psoriasis arthropathy.
Background PsA susceptibility genes are not yet clear. Recently psoriasis GWAS has successfully identified psoriasis susceptibility loci, and the relationship between most loci and PsA is unknown.
Objective to investigate the association of psoriasis susceptibility loci in PsA, PsC, psoriasis cutaneous only, and control samples found in GWAS research.
Methods the genotyping was carried out on the Sequenom platform in 379 cases of PsA, 595 PsC and 1181 cases, and the correlation analysis was carried out by Cochran-Armitage trend test. Cochran's Q and I~2 methods were used to analyze the heterogeneity between PsA and PsC, and PsA and peripheral joint type PsA.
Results the ERAP1 gene (rs151823, P =2.82 x 10~ (-6), OR=1.47) and IL28RA gene (rs4649203, P =6.14 10~) were found to be related to the gene. P =4.20 * 10~ (-7), OR=1.52) and PsA, also in PTTG1, IL1, NOS2, IL23A and so on. The correlation between (rs2546890, p= 5.21E * 10~ (-4), OR=1.28) and PsC. Heterogeneity analysis found that PsA and PsC exist in the ZNF816A gene (Q test P value is 0.04).
Conclusion ERAP1, IL28RA, GJB2, TNIP1, IL12B and other genes are common susceptibility genes of PsA and PsC..ZNF816A gene may be a susceptible gene of PsC, and has nothing to do with PsA.
The second chapter is based on ankylosing spondylitis, rheumatoid arthritis GWAS results based on psoriasis arthropathy susceptibility genes.
Background PsA and ankylosing spondylitis and rheumatoid arthritis have some common features in clinical manifestation and histopathology, and previous studies have confirmed that these diseases cross between susceptible genes.
Objective to study the genotyping and correlation of SNP loci of the susceptible gene of ankylosing spondylitis in PsA, PsC and control samples in the recent GWAS study.
Methods a total of 36 SNP regions of 29 regions were selected for genotyping in 379 cases of PsA, 595 PsC and 806 healthy controls. Correlation analysis was performed by Cochran-Armitage trend test. The heterogeneity of PsA and PsC, and spinal PsA and peripheral joint PsA were analyzed by Cochran's Q and I2 test.
Results the susceptibility gene ERAP1 (rs27037, p=6.66 * 10~ (-5), OR=1.43) and the susceptible region 21q22.2 (RS rs2242944, P=1.07 x 10~ (-3)) are significantly related. The susceptibility gene KIF5A-PIP4K2C (rs1678542, p=3.66 x 10~ (-2), OR=0.81) with PsA has the associated signal that.ERAP1 gene and PsC are also significantly related to.21q22.2 region, IL23R gene and PsC without correlation analysis show that the susceptible gene of ankylosing spondylitis is associated with the spinal column. 1.52, There was no positive significance (p=5.53 x 10~ (-1), OR=1.07) in only peripheral arthritis (PsA). The susceptibility genes of rheumatoid arthritis (AFF3), KIF5A-PIP4K2C, 7q32.3 area and peripheral joint type PsA group were suggested to be related signals, not related to the spinal group.
Conclusion the ERAP1 gene is PsA, PsC and ankylosing spondylitis common susceptible gene.21q22.2 region is the common locus of PsA and ankylosing spondylitis. The spinal PsA and ankylosing spondylitis may have some common genetic background, but the peripheral joint PsA may have the common genetic background with the rheumatoid arthritis.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R758.63
本文編號：2133654
[Abstract]:Part one epidemiological and clinical characteristics of psoriasis arthropathy
Chapter one: the constituent ratio and clinical characteristics of psoriasis arthropathy in psoriasis
Background foreign studies have shown that PsA (psoriatic arthritis) accounts for approximately 6-48% in patients with psoriasis. In China, the National Psoriasis epidemiological survey in 1984 showed that PsA accounted for only 0.69%. in psoriasis.
Objective to study the constituent ratio (prevalence) and clinical characteristics of PsA in psoriasis.
Methods a cross-sectional study was carried out in the Department of dermatology in the Department of dermatology to screen the prevalence of PsA in adult patients with psoriasis, and to register the clinical data. The research methods were combined with the joint situation questionnaire, physical examination, imaging examination, and the methods of consultation in the Department of rheumatism, and were diagnosed by the standard of CASPAR. The registration contents include sex, age, and silver chip. Age, time of disease, type of skin lesion, condition and severity, location of the disease, family history of psoriasis, time of onset of involvement of joints, morbidity and physical examination, auxiliary examination results, etc.
Results a total of 1928 patients were enrolled in this study, of which 256 (13.3%) patients with joint symptoms were examined with corresponding physical examination and X-ray, CT, and high frequency ultrasound. For 160 patients with joint symptoms but not previously diagnosed by a department of rheumatism doctor, the Department of rheumatism consultation was requested to exclude other joint lesions. According to the diagnosis of CASPAR A total of 112 patients with PsA were identified, accounting for 5.8% of all psoriasis patients, of which 103 patients (92%) were first diagnosed with.PsA with inflammatory peripheral arthritis, 30 (26.8%) with spinal involvement, 30 (26.8%) patients (26.8%) with attachment point inflammation (10.7%), the peripheral joints and spinal joints were involved in.PsA relative characteristics. Sexual distal interphalangeal arthritis and finger / phalanges were compared in 27 (24.1%) and 15 (13.4%) patients with.PsA and non PsA psoriasis. The age of PsA patients was slightly older (44.9 vs.35.5 years). The age of the lesions was slightly late (30.8 vs. 27.7 years old), and the proportion of late psoriasis (late at 40 years old) was slightly higher than that of the late type of psoriasis. The course of psoriasis in non PsA patients (23.2% vs.15.6%) was longer than that of non PsA patients (14.1 vs 7.8 years), the PASI score (9.68 vs. 6.01) and the proportion of skin lesions with erythroderma (4.5% vs. 0.9%) were higher than those in non PsA patients, and the proportion of nail damage (46.4% vs. 21%) and head skin damage was also higher than that of non PsA patients (90.2% vs. 76.4%).
Conclusion PsA is 5.8% of psoriasis patients. It is not rare in psoriasis patients and most of the patients are in a missed diagnosis. Doctors in the General Department of Dermatology should improve the importance and understanding of the disease, and diagnose and treat patients accurately and prevent the occurrence of malformation.
The second chapter is a rare clinical type of psoriasis arthropathy.
Clinical analysis of 22 cases of SAPHO syndrome in the first section
Background SAPHO syndrome is synovitis, acne, impetigo, osteosarc and osteitis syndrome. There is a cross between PsA and the disease.
Objective to study the clinical characteristics of the disease.
Methods the clinical data of 22 patients with SAPHO syndrome were registered and analyzed.
Results there were 7 males and 15 females. The average age of skin lesions was 45 years old and the average age of bone and joint involvement was 44 years. There were 21 cases of palmar and plantar pustular disease and 1 cases of fulminant acne. 19 cases of anterior chest wall involvement in bone joint involvement, 4 cases of peripheral joint and 2 cases of sacroiliac joint involvement in the joint involvement, 10 cases of joint involvement earlier than skin lesions, 9 cases. The lesions were earlier than the joint involvement. The lesions and joint involvement occurred in 3 patients. The average interval between joint involvement and skin lesions was 2.7 years, the longest being 20 years.
Conclusion SAPHO syndrome in Department of dermatology is more common in middle-aged women than in women. Palmoplantar impetigo and anterior chest wall bone and joint involvement are the most common clinical manifestations.
Analysis of 14 cases of second cases of distal interphalangeal arthritis type psoriasis
Background distal interphalangeal predominant (DIP) PsA is relatively rare in clinic.
Objective to study the clinical characteristics of DIP type PsA.
Methods the clinical data of outpatients with PsA were registered, and the clinical data of 14 PsA patients with the initial type DIP were analyzed.
Results the average age of onset was 41 years (23~59 years), male: female: all patients with 4:3. were earlier than arthritis, with an average interval of 13 years. All the patients were involved in the scalp, and 10 cases (71.4%) were involved in the joint finger / toe with nail damage. With the progress of the disease, 8 patients in the 14 cases were affected by other joints outside the DIP joint. There was also a change in the type of bed..10 patients were misdiagnosed, and the average time to delay diagnosis was 6 years.
Conclusion the lesion of skin lesions early in arthritis, scalp damage and DIP type PsA closely related to.PsA clinical classification changes with time, the significance of clinical classification of Moll and Wright needs further study. The clinical misdiagnosis and delayed diagnosis of the disease are serious, the general doctors need to improve the understanding of the disease.
The second part is the susceptibility gene of psoriasis arthropathy.
Chapter one is based on psoriasis GWAS findings and the susceptibility genes of psoriasis arthropathy.
Background PsA susceptibility genes are not yet clear. Recently psoriasis GWAS has successfully identified psoriasis susceptibility loci, and the relationship between most loci and PsA is unknown.
Objective to investigate the association of psoriasis susceptibility loci in PsA, PsC, psoriasis cutaneous only, and control samples found in GWAS research.
Methods the genotyping was carried out on the Sequenom platform in 379 cases of PsA, 595 PsC and 1181 cases, and the correlation analysis was carried out by Cochran-Armitage trend test. Cochran's Q and I~2 methods were used to analyze the heterogeneity between PsA and PsC, and PsA and peripheral joint type PsA.
Results the ERAP1 gene (rs151823, P =2.82 x 10~ (-6), OR=1.47) and IL28RA gene (rs4649203, P =6.14 10~) were found to be related to the gene. P =4.20 * 10~ (-7), OR=1.52) and PsA, also in PTTG1, IL1, NOS2, IL23A and so on. The correlation between (rs2546890, p= 5.21E * 10~ (-4), OR=1.28) and PsC. Heterogeneity analysis found that PsA and PsC exist in the ZNF816A gene (Q test P value is 0.04).
Conclusion ERAP1, IL28RA, GJB2, TNIP1, IL12B and other genes are common susceptibility genes of PsA and PsC..ZNF816A gene may be a susceptible gene of PsC, and has nothing to do with PsA.
The second chapter is based on ankylosing spondylitis, rheumatoid arthritis GWAS results based on psoriasis arthropathy susceptibility genes.
Background PsA and ankylosing spondylitis and rheumatoid arthritis have some common features in clinical manifestation and histopathology, and previous studies have confirmed that these diseases cross between susceptible genes.
Objective to study the genotyping and correlation of SNP loci of the susceptible gene of ankylosing spondylitis in PsA, PsC and control samples in the recent GWAS study.
Methods a total of 36 SNP regions of 29 regions were selected for genotyping in 379 cases of PsA, 595 PsC and 806 healthy controls. Correlation analysis was performed by Cochran-Armitage trend test. The heterogeneity of PsA and PsC, and spinal PsA and peripheral joint PsA were analyzed by Cochran's Q and I2 test.
Results the susceptibility gene ERAP1 (rs27037, p=6.66 * 10~ (-5), OR=1.43) and the susceptible region 21q22.2 (RS rs2242944, P=1.07 x 10~ (-3)) are significantly related. The susceptibility gene KIF5A-PIP4K2C (rs1678542, p=3.66 x 10~ (-2), OR=0.81) with PsA has the associated signal that.ERAP1 gene and PsC are also significantly related to.21q22.2 region, IL23R gene and PsC without correlation analysis show that the susceptible gene of ankylosing spondylitis is associated with the spinal column. 1.52, There was no positive significance (p=5.53 x 10~ (-1), OR=1.07) in only peripheral arthritis (PsA). The susceptibility genes of rheumatoid arthritis (AFF3), KIF5A-PIP4K2C, 7q32.3 area and peripheral joint type PsA group were suggested to be related signals, not related to the spinal group.
Conclusion the ERAP1 gene is PsA, PsC and ankylosing spondylitis common susceptible gene.21q22.2 region is the common locus of PsA and ankylosing spondylitis. The spinal PsA and ankylosing spondylitis may have some common genetic background, but the peripheral joint PsA may have the common genetic background with the rheumatoid arthritis.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R758.63
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