本文選題：尋常型銀屑病　切入點：肥胖　出處：《安徽醫(yī)科大學(xué)》2010年博士論文　論文類型：學(xué)位論文

【摘要】： 第一部分:超重、肥胖與成人尋常型銀屑病臨床表現(xiàn)的相關(guān)性研究 背景 銀屑病不僅是一個皮膚疾病,而且是一個慢性炎癥性疾病,并且和多個系統(tǒng)性疾病相關(guān)。臨床觀察研究證實尋常型銀屑病患者容易伴發(fā)多個系統(tǒng)性疾病。有研究發(fā)現(xiàn)尋常型銀屑病患者的肥胖率高于一般人群,而且病情輕重和體重指數(shù)相關(guān)。分子生物學(xué)研究表明尋常型銀屑病與其他系統(tǒng)性疾病可能存在共同的發(fā)病機制通路。 目的 在漢族人中探討超重和肥胖與尋常型銀屑病臨床表現(xiàn)的關(guān)系,評價超重和肥胖對銀屑病臨床表現(xiàn)的作用。為從預(yù)防醫(yī)學(xué)和臨床醫(yī)學(xué)角度深入認(rèn)識尋常型銀屑病的病因及發(fā)病機制,提供科學(xué)依據(jù)。 方法 采用醫(yī)院為基礎(chǔ)的病例-對照研究方法,對尋常型銀屑病病例與對照的資料進行橫斷面的病例對照分析。病例和對照來源于中國中部地區(qū)多個醫(yī)院的皮膚科門診。收集資料包括年齡、性別、身高、體重、發(fā)病年齡、皮損累及部位、疾病嚴(yán)重程度、家族史情況等。對照來源與病例相同地區(qū)的健康體檢人群或門診的其他皮膚病患者。病例和對照均為滿18歲的成人。尋常型銀屑病患者與健康對照的超重和肥胖比較根據(jù)不同數(shù)據(jù)類型使用了t檢驗、卡方檢驗。體重指數(shù)與銀屑病嚴(yán)重程度的相關(guān)性評價使用Pearson相關(guān)性檢驗。OR值和p值使用logistic回歸分析計算。 結(jié)果 本研究中的銀屑病患者共計4452人,平均年齡36.54±13.08歲。患者中有男性2561人(57.52%),女性1891人(42.48%)。對照共計1166人,平均年齡36.69±13.75歲。男性668 (57.28%)人,女性498 (42.72%)人。成人銀屑病患者中超重和肥胖的發(fā)生率分別為23%和4.02%。與對照相比,成人尋常型銀屑病患者伴發(fā)超重和肥胖的比例顯著性增高,OR值分別為1.301 (1.105-1.531)和1.680 (1.134-2.491)。年齡30-45歲和45歲以上組銀屑病患者的超重和肥胖的發(fā)生率要高于年齡30歲的患者,組間存在統(tǒng)計學(xué)差異(p0.01)。中度和重度的銀屑病患者超重和肥胖的發(fā)生率高于病情較輕的銀屑病患者(p0.01)。其危險度分別是病情較輕患者的6.77倍(中度病情)和5.62倍(重度病情)。疾病的嚴(yán)重程度(PASI)與體重指數(shù)呈現(xiàn)正相關(guān)(BMI比PASI,r=0.184, P0.01)。BMI≥25的超重和肥胖病例較BMI25正常體重的患者更容易累及手、腳、臀部、軀干和四肢(P0.01)。 結(jié)論 漢族成人尋常型銀屑病的超重和肥胖的發(fā)病率高于正常對照。伴發(fā)超重和肥胖的成人銀屑病患者的病情比體重正常的成人銀屑病患者嚴(yán)重,病情嚴(yán)重程度和體重指數(shù)呈正相關(guān)。超重和肥胖的成人銀屑病患者的皮損更容易累及手、腳、臀部、軀干和四肢。 第二部分:超重、肥胖與兒童尋常型銀屑病臨床表現(xiàn)的相關(guān)性研究 背景 銀屑病是常見的慢性炎癥性皮膚病,可累及任何年齡段的人群。兒童尋常型銀屑病較成人銀屑病有其自身的臨床特點,如常有家族史、容易發(fā)生點滴型銀屑病等。近年來,中國兒童肥胖的發(fā)生率較前迅速增加。國外有研究提示,與成人的結(jié)果相似,肥胖與兒童銀屑病的發(fā)病相關(guān)。 目的 在漢族人中探討超重和肥胖與兒童尋常型銀屑病臨床表現(xiàn)的關(guān)系,評價超重和肥胖對兒童尋常型銀屑病臨床表現(xiàn)的作用。 方法 采用醫(yī)院門診收集的臨床資料,對332例兒童尋常型銀屑病病例進行分析。收集資料包括年齡、性別、身高、體重、發(fā)病年齡、皮損累及部位、疾病嚴(yán)重程度、家族史情況等。本研究采用累積logit模型分析性別、年齡、發(fā)病年齡、家族史及肥胖對兒童尋常型銀屑病病情嚴(yán)重程度(PASI)的影響,統(tǒng)計軟件使用SPSS軟件10.0包含累積logit模型的模塊進行計算。體重指數(shù)與銀屑病嚴(yán)重程度的相關(guān)性評價使用Spearman相關(guān)性檢驗。 結(jié)果 本次研究共包括了332名兒童尋常型銀屑病患者,平均年齡是11.3±2.69歲,平均發(fā)病年齡為9.83±2.98歲(10個月-15歲)。患者的數(shù)量隨著年齡增長而逐漸增加。兒童尋常型銀屑病超重和肥胖的比例分別為15.66%和9.04%。發(fā)病年齡在小于10歲組的病情比10-15歲組的嚴(yán)重,差異有統(tǒng)計學(xué)意義(P0.01)。病情較重的危險度是10-15歲組的7.13倍。超重和肥胖兒童患者較體重正常兒童患者的病情更加嚴(yán)重(P0.01)。伴發(fā)超重和肥胖的兒童患者分別是體重正常的兒童患者發(fā)病較重的危險度的2.48倍和3.46倍。疾病的嚴(yán)重程度與體重指數(shù)呈現(xiàn)正相關(guān)。 結(jié)論 年齡較小的患者和發(fā)病年齡較早的兒童尋常型銀屑病患者有重癥的傾向。超重和肥胖兒童尋常型銀屑病患者比體重正�；颊叩牟∏閲�(yán)重,而且病情嚴(yán)重程度和體重指數(shù)存在相關(guān)性。 第三部分rs1265181與BMI對尋常型銀屑病的交互影響及遺傳易感位點對尋常型銀屑病伴發(fā)超重和肥胖表型的作用 背景 尋常型銀屑病是常見的慢性炎癥性皮膚病,是多種環(huán)境與遺傳因素共同作用的結(jié)果。大量研究表明HLA的等位基因、超重和肥胖與尋常型銀屑病密切相關(guān)。最近在中國人群中進行的全基因組關(guān)聯(lián)分析發(fā)現(xiàn)rs1265181是HLA區(qū)域中最顯著的SNP,并且能夠代表PSORS1的關(guān)聯(lián)信號。但是,rs1265181與超重和肥胖交互作用對銀屑病的影響尚不清楚。最近同時幾篇發(fā)表的銀屑病全基因組關(guān)聯(lián)分析發(fā)現(xiàn)了數(shù)個銀屑病相關(guān)的易感位點,但是這些位點在尋常型銀屑病伴發(fā)超重和肥胖發(fā)病機制中的作用尚不得而知。 目的 在前期研究數(shù)據(jù)的基礎(chǔ)上,分析rs1265181與BMI之間交互作用對尋常型銀屑病發(fā)病的影響。同時探究全基因關(guān)聯(lián)分析報道的銀屑病易感位點對銀屑病伴發(fā)超重肥胖的遺傳學(xué)作用。 方法 采用之前報道的中國人銀屑病全基因組關(guān)聯(lián)分析的rs1265181的分型數(shù)據(jù),計算分別在累加模式、隱性模式和顯性模式中的關(guān)聯(lián)結(jié)果,同時計算雜合子和純合子的OR值,建立了rs1265181最適合的統(tǒng)計模型。之后利用546個尋常型銀屑病病例和1058個對照分析rs1265181與BMI間的交互作用。 從之前中國人銀屑病全基因關(guān)聯(lián)分析研究獲得的覆蓋全基因SNP的分型數(shù)據(jù)中,獲得中國人和高加索人銀屑病全基因組關(guān)聯(lián)分析所發(fā)現(xiàn)易感位點HLA、LCE、IL12B、IL23R、IL23A、IL13和TNFAIP3中最顯著SNP的分型數(shù)據(jù)。計算這些SNP在銀屑病伴發(fā)超重和肥胖組及正常體重組的關(guān)聯(lián)信號和異質(zhì)性值。為研究BMI是否影響這些SNP的關(guān)聯(lián)性,我們采用分層分析的方法,用Breslow-Day檢驗檢測異質(zhì)性。 結(jié)果 我們發(fā)現(xiàn)顯性模型是rs1265181的關(guān)聯(lián)模式。rs1265181的CG+GG等位基因型的攜帶者BMI≥25時,患銀屑病的危險性是rs1265181的CC等位基因型的攜帶者體重正常時的46.25倍(p0.01)。 結(jié)果發(fā)現(xiàn)rs4085613 (LCE)、rs1265181(HLA)和rs2201841(IL23R)對伴發(fā)肥胖和超重銀屑病的作用要比體重正常的作用小,但是兩組間沒有差異。rs3213094(IL12B)和rs610604(TNFAIP3)對伴發(fā)肥胖和超重銀屑病的作用要比體重正常的作用大,但是兩組間沒有差異。 結(jié)論 尋常型銀屑病發(fā)病過程中rs1265181與BMI呈現(xiàn)出交互作用。未發(fā)現(xiàn)HLA、LCE、IL12B、IL23R、IL23A、IL13和TNFAIP3易感位點中最顯著的SNP對尋常型銀屑病伴發(fā)超重和肥胖與正常體重尋常型患者間的遺傳學(xué)作用存在明顯不同。
[Abstract]:Part one: a study of the correlation between overweight, obesity and the clinical manifestation of adult psoriasis vulgaris
background
Psoriasis is not only a skin disease, and is a chronic inflammatory disease, and multiple systemic diseases. Clinical study confirmed that patients with psoriasis vulgaris easily associated with multiple systemic diseases. Studies have found that patients with psoriasis vulgaris obesity rates higher than the general population, and the severity of the disease is associated with body mass index molecular biology research shows that psoriasis vulgaris and other system disorders may share the common pathways.
objective
To explore the relationship between overweight and obesity and clinical manifestations of psoriasis vulgaris, and to evaluate the effect of overweight and obesity on psoriasis clinical manifestations. To provide a scientific basis for further understanding the etiology and pathogenesis of psoriasis vulgaris from the perspective of preventive medicine and clinical medicine.
Method
Control study methods hospital based case control, cross sectional analysis of cases of psoriasis vulgaris patients and controls. Cases and controls from multiple areas of Central Hospital Chinese the outpatient department of dermatology. Data were collected including age, gender, height, weight, age, skin involvement, the severity of the disease. Family history, etc. in comparison with other skin disease sources and cases of the same area of healthy people or outpatient. Cases and controls are under 18 years of age. Adult patients with psoriasis vulgaris and healthy control of overweight and obesity according to different types of data using t test, chi square test to evaluate the correlation between body weight. Index and severity of psoriasis using Pearson correlation test,.OR value and P value were calculated using logistic regression analysis.
Result
In this study of psoriasis patients with a total of 4452 people, average age 36.54 + 13.08 years. There are 2561 male patients (57.52%), 1891 female (42.48%). In a total of 1166 people, average age 36.69 + 13.75 years old. 668 male (57.28%), 498 female (42.72%). Adult patients with psoriasis disease incidence of overweight and obesity were 23% and 4.02%. compared with the control group, adult patients with psoriasis vulgaris with proportion of overweight and obesity increased significantly, the OR values were 1.301 (1.105-1.531) and 1.680 (1.134-2.491). The age is 30-45 years old and above 45 years old group of psoriasis patients the incidence of overweight and obesity higher than the age of 30 patients, there was significant difference between groups (P0.01). Moderate and severe psoriasis patients the incidence of overweight and obesity is higher than patients with mild psoriasis patients (P0.01). The risk was 6.77 times in patients with mild (moderate condition) And 5.62 times (severe). The severity of the disease (PASI) was positively correlated with body mass index (BMI PASI, r=0.184, P0.01).BMI = 25 overweight and obese patients compared with BMI25 patients with normal body weight more easily affects the hands, feet, hips, trunk and limbs (P0.01).
conclusion
The incidence of psoriasis vulgaris in Han adult overweight and obesity rate is higher than the normal control group. With severe psoriasis and adult obesity overweight disease than normal weight of adult patients with psoriasis, the severity of the disease was positively associated with body mass index. The lesions of overweight and obese adults psoriasis patients were more likely to be involved in hands, feet, hips, the trunk and extremities.
The second part: the study of the correlation between overweight, obesity and the clinical manifestation of psoriasis vulgaris in children
background
Psoriasis is a common chronic inflammatory skin disease, can affect people of any age. Children with psoriasis vulgaris psoriasis than in adults with clinical features of its own, such as family history, prone to guttate psoriasis. In recent years, the incidence of obesity among children China is increasing rapidly. Overseas studies have suggested, and adults have similar results, related to obesity and juvenile psoriasis vulgaris.
objective
Objective to explore the relationship between overweight and obesity and clinical manifestations of psoriasis vulgaris in children in Han nationality, and to evaluate the effect of overweight and obesity on the clinical manifestations of psoriasis vulgaris in children.
Method
The clinical data of hospital outpatient collected, 332 cases of children with psoriasis vulgaris were analyzed. Data were collected including age, gender, height, weight, age, skin involvement, disease severity, family history and so on. This research adopts cumulative logit model to analyze the gender, age, age of onset, family history and obesity severity of children with psoriasis vulgaris (PASI) effect, the use of statistical software SPSS software contains 10 cumulative logit model were calculated. Correlation between body mass index and psoriasis severity evaluation using the Spearman correlation test.
Result
The study included 332 children with psoriasis vulgaris, the average age is 11.3 + 2.69 years old, the average age was 9.83 + 2.98 years (10 months -15 years). The number of patients increased gradually with age. The proportion of children with psoriasis vulgaris of overweight and obesity were 15.66% and 9.04%. respectively. The age of onset in less than 10 years old group of illness than 10-15 years was serious, the difference was statistically significant (P0.01). The serious condition of the risk is 7.13 times the 10-15 year old group. Children who are overweight or obese patients than in patients with normal weight children more serious illness (P0.01). Children with overweight and obese patients respectively. 2.48 times the risk of disease in children with normal weight heavier degree and 3.46 times. The severity was positively correlated with body mass index of disease.
conclusion
Patients with younger age and earlier onset children had severe tendency to psoriasis vulgaris. Overweight and obese children with psoriasis vulgaris were more severe than normal weight patients, and the severity of disease was correlated with body mass index.
The interaction of rs1265181 and BMI in psoriasis vulgaris and the effect of genetic susceptibility loci on the overweight and obesity phenotype of psoriasis vulgaris in the third part
background
Psoriasis is a common chronic inflammatory skin disease, is the interaction of a variety of environmental and genetic factors. The results of a large number of studies show that HLA allele, overweight and obesity related to psoriasis vulgaris. Recent genome-wide association in China population analysis found that rs1265181 is SNP the most significant HLA region. The correlation signal which can represent the PSORS1. But the effect of rs1265181 interaction with overweight and obesity on psoriasis is not clear. At the same time, several recently published psoriasis genome-wide association analysis found a number of psoriasis susceptibility loci, but these loci in psoriasis associated with overweight and obesity in the pathogenesis of still can make nothing of it.
objective
On the basis of previous studies, we analyzed the interaction between rs1265181 and BMI on the pathogenesis of psoriasis vulgaris, and explored the genetic role of psoriasis susceptible loci in psoriasis associated overweight and obesity.
Method
Type of data analysis using previously reported Chinese psoriasis genome-wide association rs1265181, calculated respectively in the accumulation mode, the association and the dominant recessive pattern model, and calculate the heterozygous and homozygous OR, established a statistical model of rs1265181 most suitable. After using 546 and 1058 cases of psoriasis vulgaris a comparative analysis of the interaction between BMI and rs1265181.
From the previous Chinese psoriasis gene association study for covering the whole of SNP genotyping data, obtained Chinese and Caucasian psoriasis genome-wide association analysis found susceptibility loci of HLA, LCE, IL12B, IL23R, IL23A, genotype data of the most significant SNP IL13 and TNFAIP3. The calculation of these SNP associated with overweight and obese group and normal weight group correlation signal and the heterogeneity of value in psoriasis. To study whether BMI affect the relevance of these SNP, we adopt the method of using Breslow-Day to test heterogeneity.
Result
We found that the dominant mode of rs1265181 model is the.Rs1265181 Association of CG+GG allele carriers when BMI is greater than 25, the risk of psoriasis is 46.25 times with normal weight rs1265181 CC allele at (P0.01).
The results showed that rs4085613 (LCE), rs1265181 (HLA) and rs2201841 (IL23R) for patients with obesity and overweight psoriasis than in the normal weight function is small, but there is no difference between the two groups (.Rs3213094 IL12B) and rs610604 (TNFAIP3) for patients with obesity and overweight psoriasis than normal weight function however, there is no difference between the two groups.
conclusion
Rs1265181 and BMI in the pathogenesis of psoriasis vulgaris showed interaction. HLA was not found, LCE, IL12B, IL23R, IL23A, IL13 and TNFAIP3 SNP are the most significant predisposing loci associated with overweight and obesity and normal weight patients with vulgaris between genetic effect on psoriasis vulgaris in different.

【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2010
【分類號】：R758.63

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