The Effects Of Interaction Between HLA-Cw6 And Environmental Factors On Psoriasis Vulgaris

PartⅠ:The Association of HLA-Cw6 and Related Haplotypes with Psoriasis VulgarisBackground Psoriasis is a disease based on complex genetic background and is related to many susceptible locus and genes.The results from various populations verified that HLA-Cw6 is a major risk factor in psoriasis vulgaris.Further,the haplotypes related to HLA-Cw6,specially in HLA-I gene,may also play an important role in psoriasis vulgaris,which was hardly studied.Although several researches suggested the differences of clinic features between HLA-Cw6~+ and HLA-Cw6~- cases,it is completely unclear that effect of the genetic heterogeneity on clinic heterogeneity in psoriasis vulgaris. Objective To explore the effects of HLA-Cw6,HLA-B57 and HLA-B13 on psoriasis vulgaris and the relationship of HLA-Cw6-B57 and HLA-Cw6-B13 haplotypes with psoriasis vulgaris;To compare various clinic features between HLA-Cw6 and HLA-Cw6,HLA-Cw6-B57 and HLA-Cw6-B13 haplotype,presenting the effects of the genetic heterogeneity on clinic heterogeneity in psoriasis vulgaris.Methods With only-case study and tradition case-control study,the case and control were selected and the collected data including questionnaires,and sample of peripheral venous blood from which the DNA was extracted by improved method.The genes were tested and typed by PCR-SSP method(polymerase chain reaction sequence specific primer,PCR-SSP).To explore role of HLA-Cw6,HLA-Cw6-B57 and HLA-Cw6-B13 haplotype in the development of psoriasis,the relationship between psoriasis and each factor was assessed in contingency tables,with T-test or X~2-test used to determine statistical significance.Mantel-Haenszel test for homogeneity was used to compute odds ratios(OR) and 95%confidence intervals(CI) for psoriasis after stratification by selected factors,or if the data were sparse,a Fisher exact test was used.With psoriasis as a dependent variable,non-condition logistic regress model in SAS statistical software package,version 9.0(SAS Institute Inc,Cary,North Carolina) was used in the multivariate analyses to adjust for potential confounding factors.ORs and 95%CIs were calculated as estimates of the relative risk for variables.The statistical significant level is a two-sided a of 0.05 for all tests.Results The results display that both of HLA-Cw6 and HLA-B57 increased the risk of psoriasis vulgaris,OR is 6.44 and 2.43(all p＜0.01),respectively,the effect of HLA-Cw6 on psoriasis is greater in female than male(OR,7.45 vs 5.73,all p＜0.01) while the effect of HLA-B57 on psoriasis is greater in male than female(OR,3.07 vs 2.00,all p＜0.01),and the effect of HLA-Cw6 is greater on earlier psoriasis than later psoriasis(7.16 vs 5.12,all p＜0.01).However,the effect of HLA-B13 on psoriasis vulgaris is not found.The linkage disequilibrium is declared between HLA-Cw6 and HLA-B57 or HLA-B13,and both of HLA-Cw6-B57 and HLA-Cw6-B13 were the risk haplotypes of psoriasis vulgaris,OR is 6.84 and 3.17(all p＜0.01),respectively.The effect of HLA-Cw6-B57 on psoriasis is greater for male than female(OR,8.85 vs 5.71, all p＜0.01),in contrast,the effect of HLA-Cw6-B13 on psoriasis in female than male(OR,3.54 vs 2.89,all p＜0.01),but the effect of two risk haplotypes were all greater on earlier psoriasis than later psoriasis.Compared with HLA-Cw6~- cases,the onset age of psoriasis with HLA-Cw6 is significantly earlier in female than male(p＜0.05).The psoriasis vulgaris with HLA-Cw6 shown those features for earlier onset,more many affected positions,more serious,much more in winter but those difference is not significant in statistics(all p＞0.05),the difference of clinic features between HLA-Cw6-B57 and HLA-Cw6-B13 haplotype is not significant(p＞0.05).Conclusions First,HLA-Cw6 and HLA-B57 were the risk genes of psoriasis vulgaris, but the effect of HLA-B13 genes on psoriasis vulgaris is not obvious.Second,the linkage disequilibrium between HLA-Cw6 and HLA-B57 or HLA-B13 was validated, all increasing the risk of psoriasis vulgaris.Third,The psoriasis vulgaris with HLA-Cw6 showed those features for earlier onset,more many affected positions,more serious, much more in winter but those difference is not significant.PartⅡ:The effects of interaction between HLA-Cw6 and endogenesis and xenobiotic factors on psoriasis vulgarisBackground Psoriasis is a chronic inflammatory skin disease,which results from the common effects of multiply environmental and genetic factors.It was well known that HLA-Cw6,cigarette smoking and life stress events was closely related to psoriasis vulgaris.Further,the recent results declared that higher waist-hip ratio(WHR) and body mass index(BMI) may increase the risk of psoriasis vulgaris.But,to our knowledge,no evidence of interaction between HLA-Cw6 and in turn,BMI,WHR and cigarette smoking are available.Objective To mainly analyzed the interaction between HLA-Cw6 and in turn BMI, WHR and cigarette smoking in psoriasis vulgaris.The data is obvious significance for preventive and clinical medicine.Methods 466 patients and 178 controls received this epidemiological investigation and HLA typing by PCR-SSP based on the hospital-based case-control study,and the data was analyzed by non-condition logistic regress model.Results There was a graded positive association of WHR and BMI with psoriasis vulgaris.Compared with a WHR of 0.80 or less than 0.80,the OR was 2.36(p＜0.01) for WHR 0.80-0.85,and 2.74(p＜0.01) for WHR greater than 0.85.Compared with subjects with a BMI of 20 or less than 20,the multivariate OR of psoriasis were 1.20(p＞0.05) for a BMI of 20-25,1.84(p＜0.05) for a BMI of more than 25 corresponding overweight (p for trend,＜0.01).We found not only the risk of psoriasis for the individual with HLA-Cw6 was 8.33 times greater than that for individual without HLA-Cw6 but also the risk increased approximately 35 times in individuals with HLA-Cw6 and a overweight as compared with one without HLA-Cw6 and a non-overweight,and 17-fold when the individuals with HLA-Cw6 and a WHR of more than 0.80 were compared with individuals without HLA-Cw6 and a WHR of 0.80 or less than 0.80, displaying the combined effect of HLA-Cw6,BMI and WHR(all p＜001).The data of 178 cases and 178 controls showed that the risk of psoriasis was related to smoking,the adjusted OR being 2.07(P＜0.01),and there is a graded positive association between the risk of psoriasis and intensity or duration of smoking.Stressful life events increased the risk of psoriasis(OR=7.87,P＜0.01).We found the waist-hip ratio(WHR) increased the risk of psoriasis vulgaris and OR was 2.67(P＜0.01) in China. Individuals harboring the HLA-Cw6 gene obviously increased the risk of psoriasis,OR being 9.93(P＜0.01) after adjusted for potential confounder factors while the OR of psoriasis for HLA-B57 was 2.41(P＜0.05).Significant interacion between HLA-Cw6 and HLA-B57 for psoriasis was found(OR=10.51,P＜0.01).A striking finding is that the risk of psoriasis for smokers with HLA-Cw6 increased about 11-fold than non-smoker without HLA-Cw6,and the risk increased some 20-fold in individuals with HLA-Cw6 having stressful life events as compared with one without HLA-Cw6 and stressful life events.Conclusions This study suggested that HLA-Cw6,overweight,higher waist-hip ratio and cigarette smoking are material risk factors of psoriasis vulgaris,specially the combined effects of HLA-Cw6 and BMI,WHR,smoking on psoriasis vulgaris in Chinese population.