Association Study Of Psoriasis Vulgaris And Metabolic Syndrome:Epidemiology And Susceptible Genes

Background Psoriasis is a common and one of the most studied skin disease.The etiology of the disease（may influenced by multiple complex factors,such as genetic susceptibility and environmental conditions）is still not fully elucidated.In recent years,studies on psoriasis and metabolic syndrome（MS）including its components（abdominal obesity,insulin resistance,hypertension and dyslipidemia）have shown that patients with psoriasis have increased prevalence of metabolic syndrome（the components of it）.What’s more shared susceptibility loci of psoriasis and metabolic syndrome（including its components）have been reported in some ethnic groups.However,the relationship between psoriasis and the components of metabolic syndrome were shown not all the same in different regions and ethnic groups.Studies on metabolic syndrome and psoriasis are rare in China,thus a retrospective study was conducted to access the association of Psoriasis vulgaris and metabolic components（blood lipid,blood glucose,blood pressure）and validate the susceptible loci of metabolic syndrome previously reported in PsV patients of Chinese Han.Objective1.To evaluate the connection between psoriasis vulgaris and blood lipid,blood glucose,as well as blood pressure,through a hospital-based case-control study with a larger sample size.2.To validate the more significantly susceptible genes of metabolic syndrome previously reported in patients with psoriasis vulgaris of Chinese Han.3.Since HLA-C*06:02 is the major susceptible gene of psoriasis reported in the past,further stratified analysis based on HLA-C*06:02 was carried out to explore whether the selected 18SNPs have interaction with HLA-C*06:02 in Chinese patients with psoriasis vulgaris.MethodsThis study contains two parts:A total of 511 patients with psoriasis vulgaris and 543healthy controls were enrolled in the first part.The parameters of blood lipid,blood glucose and blood pressure were measured and then recorded in all the subjects.The data were analyzed with the use of SPSS20.0 statistical software.The second part of the study included1030 patients with psoriasis vulgaris and 965 healthy controls.Peripheral blood sample（anticoagulant whole blood）of the subjects were collected and then stored at-80℃.Eighteen single nucleotide polymorphisms（SNPs）loci of metabolic syndrome previously reported were selected.Genetic polymorphisms were detected using second-generation sequencing and sequence specific primer polymerase chain reaction.All the SNPs will be validated in the cases and the controls,PLINK 1.07 statistical software was used for statistical analysis.Results1.Compared with the control group,the levels of triglyceride（TG）（t=2.74,P<0.01）and total cholesterol（TCH）（t’=1.99,P<0.05）were increased in PsV patients,high density lipoprotein cholesterol（HDL-C）decreased（t’=-2.67,P<0.01）in PsVs,and low density lipoprotein cholesterol（LDL-C）levels showed no significant difference between the two groups（t’=1.69,P=0.09）.2.The prevalence of elevated fasting plasma glucose（χ²=22.19,P<0.01）,elevated blood pressure（χ²=8.03,P<0.01）and increased triglyceride（χ²=4.87,P<0.05）in PsV group were higher than those in control group.3.Seven SNPs were found significantly associated with psoriasis vulgaris.rs805303（P=0.012,OR=0.85）,rs3177928(P=1.37×10^-15,OR=2.51),rs2247056(P=3.73×10^-4,OR=0.67)located in HLA gene region.rs1047781（P=0.012,OR=1.18）,rs281379（P=0.014,OR=1.71）,rs492602（P=0.005,OR=1.86）located in FUT2 region.rs2303138（P=0.014,OR=1.18）in LNPEP region.4.After stratified analysis,rs805303（P=0.017,OR=0.74）and rs2303138（P=0.041,OR=1.30）were associated with PsVs when HLA-C*0602 was positive.When HLA-C*0602was negative rs805303(P=5.62×10^-5,OR=0.68),rs3177928（P=0.003,OR=1.75）,rs281379（P=0.034,OR=1.96）,and rs492602（P=0.025,OR=2.04）were related to PsVs.Conclusions:1.Psoriasis vulgaris is associated with the components of metabolic syndrome including dyslipidemia,.elevated fasting plasma glucose,and elevated blood pressure.2.Seven metabolic syndrome related SNPs located in HLA（rs805303,rs3177928,rs2247056）,FUT2（rs1047781,rs281379,rs492602）and LNPEP（rs2303138）genes were significantly associated with psoriasis vulgaris.3.In Chinese Han polulation with HLA-C*0602 positive,HLA（rs805303）and LNPEP（rs2303138）were associated with psoriasis vulgaris susceptibility.In the population with HLA-C*0602 negative,HLA（rs805303,rs3177928）and FUT2（rs281379,rs492602）were associated with psoriasis vulgaris susceptibility.