The Correlation Between Overweight, Obesity And Psoriasis Vulgaris And The Effects Of Genetic Susceptible Loci On Pathogenesis Of Psoriasis Vulgaris With Overweight And Obesity

Part I:The correlation between Overweight, Obesity and Psoriasis Vulgaris in Adult patientsBackgroundOver the past decade, awareness is increasing that psoriasis as a disease is more than skin deep, but a chronic inflammatory disease and that it is associated with systemic disorders. Multiple clinic observational studies have demonstrated associations between psoriasis and several comorbidities-especially obesity. Some studies indicated that more patients with psoriasis are much more likely to be obese than normal. And the severity of psoriasis is correlated with adiposity. Molecular biology research indicated that psoriasis vulgaris and other system disorders may share the common pathways.ObjectiveTo explore the relationship between obesity and psoriasis and to evaluate the obesity effect on the clinical features of psoriasis in Chinese Han population. The data is obvious provide scientific evidence of psoriasis vulgaris pathogenesis for preventive and clinical medicine.MethodsA hospital-based cross-sectional study was conducted. The study subjects were recruited from dermatology out-patient clinic of multiple hospitals mainly in central China between December 1997 and September 2009. Patients'clinical information, including age, gender, age of onset, affected sites, severity of psoriasis lesions on the skin, were recorded from the subjects through a full clinical checkup. Controls were above 18 years of age, from local unrelated subjects presenting for health examination and the other skin disease patients without psoriasis. Comparisons of overweight/obesity frequencies between psoriasis and controls were made using t-test, the Pearson'sχ2 test and odds ratios (OR). Pearson correlation coefficients were used to assess the relationship between BMI and psoriasis severity. A logistic regression analysis performed to obtain OR and p-values.ResultsThe present study involved a total of 4452 patients with psoriasis vulgaris, mean age of 36.54±13.08 years. Male patients were 2561(57.52%) and female patients were 1891(42.48%). A total of 1166 controls were involved in our study, including 668 (57.28%) males and 498 (42.72%) females. The average age of all controls was 36.69±13.75 years. The incidence of overweight and obesity in adult patients with psoriasis were 23% and 4.02% respectively. Compared to the control group, a significant greater proportion of overweight and obesity in psoriasis patients was observed (OR=1.301, 95% CI: 1.105-1.531) and (OR=1.680, 95% CI: 1.134-2.491). The incidence of overweight and obesity in aged 30-45 years group and 45 + age group of patients with psoriasis vulgaris are higher than the age <30 years patients group. There was significant difference between groups (p <0.01). The incidence of overweight and obesity in moderate and severe psoriasis vulgaris groups is higher than patients with mild psoriasis vulgaris group (p <0.01). The disease severity of psoriasis measured by PASI was statistically significantly positively associated with BMI. Trends for increasing psoriasis severity assessments with MBI were found: r =0.184, P<0.01 (BMI vs. PASI). More overweight patients affected hands or/and feet(P<1×10-4), buttocks(P< 0.01), trunk(P < 1×10-4), legs(P < 1×10-4), arms(P < 1×10-4) and arthritis(P < 1×10-4) and had no significant differences in other affected sites that we analyzed.ConclusionsOur study suggested that psoriatic adult patients have a higher prevalence of overweight and obesity compared with non-psoriatic patients in Chinese Han population. Overweight and obese adult patients have more severe conditions than normal weight patients. The disease severity of psoriasis measured by PASI was significantly positively associated with BMI. More overweight patients affected hands or/and feet, buttocks, trunk, legs and arms. Part II:The correlation between Overweight, Obesity and Psoriasis Vulgaris in Childhood patientsBackgroudPsoriasis is a frequent and burdensome chronic inflammatory disease which can involve any age group. Clinic features of juvenile psoriasis vulgaris have its own characters, including an increased rate of guttate psoriasis and more incidence of family history. In recent years, the incidence of obesity among children in China has rapidly progressed than before. Overseas studies have suggested,similar with adults, obesity and juvenile psoriasis vulgaris has correlated.ObjectiveTo explore the relationship between obesity and juvenile psoriasis vulgaris and to evaluate the obesity effect on the clinical features of juvenile psoriasis vulgaris in Chinese Han population.MethodsBy using the date from hospital out-patient, we collected and analyzed the clinic data of 332 children with juvenile psoriasis vulgaris. Patients'clinical information, including age, gender, age of onset, affected sites, severity of psoriasis lesions on the skin, were recorded from the subjects through a full clinical checkup. In the present study, the cumulative logit model was used to analysis the effect of gender, age, onset age, family history and obesity on children's psoriasis severity. The statistical software was used the SPSS including cumulative logit package. Spearman correlation coefficients were used to assess the relationship between BMI and psoriasis severity. ResultsThe present study involved a total of 332 patients with juvenile psoriasis vulgaris. The mean age was 11.3±2.69 years and average age of onset was 9.83±2.98 year. A prevalence was showed than a constant increase throughout the years 0 to 15. The incidence of overweight and obesity in patients with juvenile psoriasis vulgaris were 15.66% and 9.04% respectively. The patients below 10 year are more severe than patients in 10-15 year group. There was significant difference between groups (p <0.01) and the OR is 7.13. Overweight and obesity patients with juvenile psoriasis vulgaris is more severe than normal weight patients (P<0.01). Severe risk of Overweight and obesity patients with juvenile psoriasis vulgaris is 2.48 times and 3.46 times than normal weight patients. Trends for increasing psoriasis severity assessments with MBI were found: r =0.22, P<0.01.ConclusionsYounger and early onset juvenile psoriasis vulgaris patients had a tendency to be more severe condition. Overweight and obese children patients had more serious condition than normal weight children patient. The disease severity of psoriasis measured by PASI was statistically significantly positively associated with BMI (BMI vs. PASI, r =0.22, P<0.01). Part III: The effects of interaction between rs1265181 and overweight/obesity on psoriasis vulgaris and the genetic effect of psoriasis susceptible loci on pathogenesis of psoriasis vulgaris with overweight/obesityBackgroudPsoriasis is a chronic inflammatory skin disease, which results from the common effects of multiply environmental and genetic factors. It was well known that many alleles in HLA region, overweight and obesity were related to psoriasis vulgaris. Recently, a genome wide association study carried out in Chinese revealed that rs1265181 is the most significant SNP in HLA region and can tagged most part of association signal in PSORS1. But, to our knowledge, no evidence of interaction between rs1265181 and BMI are available. Meanwhile, several published enome wide association study found multiple susceptible loci for psoriasis. However, the genetic effects of psoriasis susceptible loci on pathogenesis of psoriasis vulgaris with overweight/obesity are unknown.ObjectiveBased on previous obtained data, we analyzed the interaction between rs1265181 and BMI in psoriasis vulgaris. Simultaneously, we investigate the genetic effects of psoriasis susceptible loci on pathogenesis of psoriasis vulgaris with overweight/obesity.MethodsBy using the rs1265181 genotype date from previously reported genome wide association analysis of psoriasis in Chinese, we analyzed the association results in additive, recessive and dominant models and OR in heterozygote and homozygote. Based on those results, we set up a fix model to rs1265181 for further calculate. Afterwards, using data from 546 psoriasis vulgaris and 1058 controls, we analyzed the interaction between rs1265181 and BMI on psoriasis.From previously reported genome wide association analysis of psoriasis in Chinese, we extracted genotype data of the most significant SNPs in reported susceptible loci (HLA, LCE, IL12B, IL23R, IL23A, IL13 and TNFAIP3) of previously published genome wide association studies. Then, we calculate the association signals and heterogeneity value of those SNPs in overweight/obesity psoriasis vulgaris patients and normal weight patients. Logistic regression analysis and OR estimates were used to find the best model. To investigate the contributions factors, we evaluated the effect of these SNP after stratifying by BMI, heterogeneity analyses by Breslow-Day tests were carried out.ResultsLogistic regression analysis and OR estimates revealed that the dominant model provided the best fit for SNP rs1265181.The patients with rs1265181 CG+GG genotype and BMI≥25, the risk of suffering psoriasis is 46.25 times than patients with rs1265181 CC genotype carriers and BMI <25(p <0.01).Genetic effect of rs4085613 and rs1265181 in obesity and overweight patients is weaker than in normal-weight patients, but there is no statistical difference between the two groups. Genetic effect of rs3213094 in obesity and overweight patients is stronger than in normal-weight patients, but no evidence for the SNP to play a differential role in two groups. Genetic effect of rs2201841 in obesity and overweight patients is weaker than in normal-weight patients, but there is no statistical difference between the two groups. Genetic effect of rs3213094 in obesity and overweight patients is stronger than in normal-weight patients, but there is no statistical difference between the two groups.ConclusionsOur study suggested that rs1265181 and BMI are material risk factors of psoriasis vulgaris. We did not find any evidence for the most significant SNPs in HLA,LCE,IL12B,IL23R,IL23A,IL13 and TNFAIP3 to play a differential role in overweight/obesity patients and normal weight patients.