超重、肥胖与寻常型银屑病临床表现的相关性研究及遗传易感位点对寻常型银屑病伴发超重和肥胖表型的作用

发布时间：2018-03-19 08:50

本文选题：寻常型银屑病　切入点：肥胖　出处：《安徽医科大学》2010年博士论文　论文类型：学位论文

【摘要】： 第一部分:超重、肥胖与成人寻常型银屑病临床表现的相关性研究背景银屑病不仅是一个皮肤疾病,而且是一个慢性炎症性疾病,并且和多个系统性疾病相关。临床观察研究证实寻常型银屑病患者容易伴发多个系统性疾病。有研究发现寻常型银屑病患者的肥胖率高于一般人群,而且病情轻重和体重指数相关。分子生物学研究表明寻常型银屑病与其他系统性疾病可能存在共同的发病机制通路。目的在汉族人中探讨超重和肥胖与寻常型银屑病临床表现的关系,评价超重和肥胖对银屑病临床表现的作用。为从预防医学和临床医学角度深入认识寻常型银屑病的病因及发病机制,提供科学依据。方法采用医院为基础的病例-对照研究方法,对寻常型银屑病病例与对照的资料进行横断面的病例对照分析。病例和对照来源于中国中部地区多个医院的皮肤科门诊。收集资料包括年龄、性别、身高、体重、发病年龄、皮损累及部位、疾病严重程度、家族史情况等。对照来源与病例相同地区的健康体检人群或门诊的其他皮肤病患者。病例和对照均为满18岁的成人。寻常型银屑病患者与健康对照的超重和肥胖比较根据不同数据类型使用了t检验、卡方检验。体重指数与银屑病严重程度的相关性评价使用Pearson相关性检验。OR值和p值使用logistic回归分析计算。结果本研究中的银屑病患者共计4452人,平均年龄36.54±13.08岁。患者中有男性2561人(57.52%),女性1891人(42.48%)。对照共计1166人,平均年龄36.69±13.75岁。男性668 (57.28%)人,女性498 (42.72%)人。成人银屑病患者中超重和肥胖的发生率分别为23%和4.02%。与对照相比,成人寻常型银屑病患者伴发超重和肥胖的比例显著性增高,OR值分别为1.301 (1.105-1.531)和1.680 (1.134-2.491)。年龄30-45岁和45岁以上组银屑病患者的超重和肥胖的发生率要高于年龄30岁的患者,组间存在统计学差异(p0.01)。中度和重度的银屑病患者超重和肥胖的发生率高于病情较轻的银屑病患者(p0.01)。其危险度分别是病情较轻患者的6.77倍(中度病情)和5.62倍(重度病情)。疾病的严重程度(PASI)与体重指数呈现正相关(BMI比PASI,r=0.184, P0.01)。BMI≥25的超重和肥胖病例较BMI25正常体重的患者更容易累及手、脚、臀部、躯干和四肢(P0.01)。结论汉族成人寻常型银屑病的超重和肥胖的发病率高于正常对照。伴发超重和肥胖的成人银屑病患者的病情比体重正常的成人银屑病患者严重,病情严重程度和体重指数呈正相关。超重和肥胖的成人银屑病患者的皮损更容易累及手、脚、臀部、躯干和四肢。第二部分:超重、肥胖与儿童寻常型银屑病临床表现的相关性研究背景银屑病是常见的慢性炎症性皮肤病,可累及任何年龄段的人群。儿童寻常型银屑病较成人银屑病有其自身的临床特点,如常有家族史、容易发生点滴型银屑病等。近年来,中国儿童肥胖的发生率较前迅速增加。国外有研究提示,与成人的结果相似,肥胖与儿童银屑病的发病相关。目的在汉族人中探讨超重和肥胖与儿童寻常型银屑病临床表现的关系,评价超重和肥胖对儿童寻常型银屑病临床表现的作用。方法采用医院门诊收集的临床资料,对332例儿童寻常型银屑病病例进行分析。收集资料包括年龄、性别、身高、体重、发病年龄、皮损累及部位、疾病严重程度、家族史情况等。本研究采用累积logit模型分析性别、年龄、发病年龄、家族史及肥胖对儿童寻常型银屑病病情严重程度(PASI)的影响,统计软件使用SPSS软件10.0包含累积logit模型的模块进行计算。体重指数与银屑病严重程度的相关性评价使用Spearman相关性检验。结果本次研究共包括了332名儿童寻常型银屑病患者,平均年龄是11.3±2.69岁,平均发病年龄为9.83±2.98岁(10个月-15岁)。患者的数量随着年龄增长而逐渐增加。儿童寻常型银屑病超重和肥胖的比例分别为15.66%和9.04%。发病年龄在小于10岁组的病情比10-15岁组的严重,差异有统计学意义(P0.01)。病情较重的危险度是10-15岁组的7.13倍。超重和肥胖儿童患者较体重正常儿童患者的病情更加严重(P0.01)。伴发超重和肥胖的儿童患者分别是体重正常的儿童患者发病较重的危险度的2.48倍和3.46倍。疾病的严重程度与体重指数呈现正相关。结论年龄较小的患者和发病年龄较早的儿童寻常型银屑病患者有重症的倾向。超重和肥胖儿童寻常型银屑病患者比体重正常患者的病情严重,而且病情严重程度和体重指数存在相关性。第三部分rs1265181与BMI对寻常型银屑病的交互影响及遗传易感位点对寻常型银屑病伴发超重和肥胖表型的作用背景寻常型银屑病是常见的慢性炎症性皮肤病,是多种环境与遗传因素共同作用的结果。大量研究表明HLA的等位基因、超重和肥胖与寻常型银屑病密切相关。最近在中国人群中进行的全基因组关联分析发现rs1265181是HLA区域中最显著的SNP,并且能够代表PSORS1的关联信号。但是,rs1265181与超重和肥胖交互作用对银屑病的影响尚不清楚。最近同时几篇发表的银屑病全基因组关联分析发现了数个银屑病相关的易感位点,但是这些位点在寻常型银屑病伴发超重和肥胖发病机制中的作用尚不得而知。目的在前期研究数据的基础上,分析rs1265181与BMI之间交互作用对寻常型银屑病发病的影响。同时探究全基因关联分析报道的银屑病易感位点对银屑病伴发超重肥胖的遗传学作用。方法采用之前报道的中国人银屑病全基因组关联分析的rs1265181的分型数据,计算分别在累加模式、隐性模式和显性模式中的关联结果,同时计算杂合子和纯合子的OR值,建立了rs1265181最适合的统计模型。之后利用546个寻常型银屑病病例和1058个对照分析rs1265181与BMI间的交互作用。从之前中国人银屑病全基因关联分析研究获得的覆盖全基因SNP的分型数据中,获得中国人和高加索人银屑病全基因组关联分析所发现易感位点HLA、LCE、IL12B、IL23R、IL23A、IL13和TNFAIP3中最显著SNP的分型数据。计算这些SNP在银屑病伴发超重和肥胖组及正常体重组的关联信号和异质性值。为研究BMI是否影响这些SNP的关联性,我们采用分层分析的方法,用Breslow-Day检验检测异质性。结果我们发现显性模型是rs1265181的关联模式。rs1265181的CG+GG等位基因型的携带者BMI≥25时,患银屑病的危险性是rs1265181的CC等位基因型的携带者体重正常时的46.25倍(p0.01)。结果发现rs4085613 (LCE)、rs1265181(HLA)和rs2201841(IL23R)对伴发肥胖和超重银屑病的作用要比体重正常的作用小,但是两组间没有差异。rs3213094(IL12B)和rs610604(TNFAIP3)对伴发肥胖和超重银屑病的作用要比体重正常的作用大,但是两组间没有差异。结论寻常型银屑病发病过程中rs1265181与BMI呈现出交互作用。未发现HLA、LCE、IL12B、IL23R、IL23A、IL13和TNFAIP3易感位点中最显著的SNP对寻常型银屑病伴发超重和肥胖与正常体重寻常型患者间的遗传学作用存在明显不同。
[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.

【学位授予单位】：安徽医科大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R758.63

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