Relationship Between GJB2 Gene And LCE Gene Cluster Polymorphism And Psoriasis Vulgaris Of Mongolian And Han Nationality In Inner Mongolia

Objective1.To determine the correlation between GJB2 gene polymorphism and psoriasis vulgaris in Inner Mongolia Han and Mongolian;2.To determine the correlation between LCE gene cluster polymorphism and psoriasis vulgaris in Inner Mongolia Han and Mongolian;3.HLA-Cw*06:02 stratification analysis was used to GJB2 the correlation between gene and LCE gene cluster polymorphism and psoriasis vulgaris in Inner Mongolia Han and Mongolian and its interaction with HLA-Cw*06:02.Methods1409 patients with psoriasis vulgaris(case group)who were admitted to the affiliated hospital of Inner Mongolia Medical University since December 2012,Including 1030cases of Han nationality,Mongolian 379 cases,healthy control 1483 cases(control group,965 Han,Mongolian 518 cases).Collect peripheral venous blood(anticoagulant whole blood)-80℃save and reserve,7 single nucleotide polymorphisms associated with psoriasis were selected(SNP),LCE(rs4085613,rs4112788,rs512208,rs1886734,rs4845454,and GJB2(rs3751385,rs72474224),Using second generation sequencing method to detect gene polymorphism;HLA-Cw*06:02 and LCE3C＿3B insertion/deletion copy number variants(LCE3C＿3B-CNV)weregenotypedusingpolymerasechain reaction-sequence-specific primers.All genetic variation typing data quality control,allele and gene frequency comparison using PLINK1.07 software,The minimum allele frequency(MAF)was compared by chi-square test(χ~2),The odds ratio of the smallest allele(OR)and its 95%confidence interval(95%CI),All statistical tests were performed using bilateral probability tests,Based onα=0.05,P<0.05 was statistically significant,R×C list chi-square test analysis LCE gene cluster region gene polymorphism haplotype.Results1.The Han population,Allelic frequencies of 7 genetic variants were found to be significantly different between case group and control group(P<0.05),rs4085613 on LCE3D(P=7.06 E-08,OR=0.6936,95%CI=0.607-0.7924),rs4112788(P=1.26 E-07,OR=0.698,95%CI=0.6107-0.7977),rs512208(P=1.50 E-06,OR=1.41,95%CI=1.225-1.622),rs1886734 on LCE3A(P=8.50 E-08,OR=0.6966,95%CI=0.6102-0.7953),rs4845454(P=4.66 E-08,OR=0.6914,95%CI=0.6056-0.7895),LCE3C＿3B-CNV(P=1.85 E-07,OR=0.7019,95%CI=0.6144-0.802),rs72474224 on the GJB2(P=0.009663,OR=1.761,95%CI=1.141-2.718).2.Of the Mongols,found that there was a significant difference in allele frequency between the case group and the control group(P<0.05),Includes rs4085613 located in LCE3D(P=0.02154,OR=0.7973,95%CI=0.6571-0.9673),LCE3A rs1886734(P=0.01129,OR=0.7806,95%CI=0.6445-0.9456),rs4845454(P=0.01149,OR=0.781,95%CI=0.6447-0.9462),LCE3C＿3B-CNV(P=0.02025,OR=0.7954,95%CI=0.6556-0.9651).3.Based on the stratified analysis HLA-Cw*06:02 Han population,The allele frequencies of 7 genetic variants found in HLA-Cw*06:02 positive samples were significantly different between the case group and the control group(P<0.05),Includes rs4085613(P=0.000282)located in the LCE3D,OR=0.63,95%CI=0.4904-0.8092),rs4112788(P=0.000322,OR=0.632,95%CI=0.4916-0.8123),rs512208(P=0.000217,OR=1.685,95%CI=1.276-2.227),LCE3A rs1886734(P=0.00054,OR=0.6438,95%CI=0.5011-0.827),rs4845454(P=0.000357),OR=0.6355,95%CI=0.4949-0.8159),LCE3C＿3B-CNV(P=0.000453),OR=0.6409,95%CI=0.4993-0.8226),GJB2 rs72474224(P=0.04348,OR=2.794,95%CI=0.9872-7.909).HLA-Cw*06:02 negative samples,found that the allele frequencies of 6 genetic variants were significantly different between the case group and the control group(P<0.05),rs4085613 including LCE3D(P=0.002893,OR=0.7524,95%CI=0.6237-0.9075),rs4112788(P=0.003379,OR=0.7552,95%CI=0.6258-0.9114),rs512208(P=0.003931),OR=1.333,95%CI=1.096-1.621),LCE3A rs1886734(P=0.001318,OR=0.7378,95%CI=0.6126-0.8885),rs4845454(P=0.001162,OR=0.7354,95%CI=0.6107-0.8855),LCE3C＿3B-CNV(P=0.001082),OR=0.7325,95%CI=0.6076-0.8831).4.Based on the stratified analysis HLA-Cw*06:02 Mongolian population,The allele frequencies of 6 genetic variants found in HLA-Cw*06:02 positive samples were significantly different between the case group and the control group(P<0.05),Includes rs4085613 located in LCE3D(P=0.01576,OR=0.7095,95%CI=0.5368-0.9379),rs4112788(P=0.02392,OR=0.7153,95%CI=0.5346-0.9571),rs512208(P=0.01626,OR=1.442,95%CI=1.069-1.946),LCE3A rs1886734(P=0.009599,OR=0.6932,95%CI=0.525-0.9152),rs4845454(P=0.009599),OR=0.6932,95%CI=0.525-0.9152),LCE3C＿3B-CNV(P=0.0153,OR=0.7077,95%CI=0.5349-0.9362).HLA-Cw*06:02 negative samples,found a significant difference in allele frequency between the case group and the control group(P<0.05),rs512208(P=0.04028,OR=0.699,95%CI=0.4959-0.9851).5.Haplotypes were constructed using genetic variants of six LCE gene clusters,found that the haplotype frequencies of the two dangerous haplotypes in the Han and Mongolian cases groups were higher than those in the corresponding control groups(P<0.05),Including hazardous haplotype H2(CCTGT-Del),Han case group(OR=1.64,95%CI=1.37-1.88),For the Mongolian case group(OR=1.271,95%CI=1.01-1.6)was higher than the control group;Dangerous haplotype H3(CCGGT-Del),Han case group(OR=1.331,95%CI=1.13-1.57),For the Mongolian case group(OR=1.31,95%CI=1.02-1.68)were higher than the corresponding control group.6.The Han population,Single fold analysis of LCE gene clusters based on HLA-Cw*06:02 stratification:it was found that the haplotype frequency of the two dangerous haplotypes in the case group was higher than that in the corresponding control group(P<0.05),Including hazardous haplotype H2(CCTGT-Del),Of the HLA-Cw*06:02 positive samples(OR=1.987,95%CI=1.45-2.72),Of HLA-Cw*06:02 negative samples(OR=1.511,95%CI=1.21-1.89);Dangerous haplotype H3(CCGGT-Del),Of the HLA-Cw*06:02 positive samples(OR=1.392,95%CI1.02-1.90),Of HLA-Cw*06:02 negative samples(OR=1.26,95%CI=1-1.59).7.The LCE gene cluster haplotype analysis based on HLA-Cw*06:02 stratification in Mongolian population:in HLA-Cw*06:02 positive samples,the frequency of risk haplotype H2(CCTGT-Del)in case group was higher than that in corresponding control group(OR=1.697,95%CI=1.21-2.38),but in HLA-Cw*06:02 negative samples,there was no significant difference between case group and its corresponding control group(P>0.05).ConclusionThe genetic variation of GJB2 gene(rs72474224)and LCE gene cluster(rs4085613、rs4112788、rs512208、rs1886734、rs4845454、LCE3C＿3B-CNV)is related to psoriasis vulgaris of Han nationality and Mongolian nationality in Inner Mongolia.HLA-Cw*06:02 positive/negative may affect the correlation between GJB2 gene,LCE gene cluster region genetic variation and psoriasis vulgaris.The risk haplotype H2(CCTGT-Del)and H3(CCGGT-Del)in LCE gene cluster area were correlated with psoriasis vulgaris of Han nationality and Mongolian nationality in Inner Mongolia,and may interact with HLA-Cw*06:02.