A Study Of Susceptible Gene For Gerneralized Pustular Psoriasis And Psoriasis Vulgaris In Chinese Han In Inner Mongolia

Objective To investigate the association between interleukin-36 receptor antagonist gene(IL36RN),caspase recruitment domain-containing protein(CARD14),tumor necrosis factoralpha-induced protein(TNFAIP3)-interacting protein 1,(TNIP1),the 1C subunit of the adaptor protein complex 1(AP1S3),human leukocyte antigen(HLA)and CSMD1 gene variation and psoriasis vulgaris(PsV)and generalized pustular psoriasis(GPP)of Han population in Inner Mongolia.Methods Totally,136 patients with generalized pustular psoriasis(GPP),1030 patients with psoriasis vulgaris and 965 healthy controls were enrolled into the study.According to previous reports,16 SNPs(except HLA-C*06:02)in 6 gene regions related to GPP and PsV were selected and amplified by polymerase chain reaction(PCR).All the above SNPs(except HLA-C*06:02)were sequenced by next generation sequencing.HLA-C*06:02 was based on PCR-SSP.With the PLINK 1.07 package,statistical analysis were carried out by using chi-square test for comparions of minimum allele frequencies(MAF%)of 16 SNPs and the frequencies of HLA-Cw*06:02 positive between the case group and the control group.The MAF%was analyzed by PLINK 1.07 statistical software for?~2 test.The allelic odds ratio(OR)and its 95%confidence interval(CI)were calculated.The difference was statistically significant(P<0.05).Result?8genelocisareassociatedwithGPP,including rs139497891(P=2.90E-04,OR=9.66,95%CI=2.15-43.39)and rs148755083(P=2.72E-80,OR=25.63,95%CI=16.26-40.39)in IL36RN gene;rs17728338(P=1.22E-16,OR=3.51,95%CI=2.57-4.79)in TNIP1 gene;rs3177928(P=3.18E-07,OR=2.66,95%CI=1.80-3.924),rs118179173(P=2.30E-02,OR=2.05,95%CI=1.09-3.836)and HLA-Cw*06:02 in HLA gene;rs3813063(P=4.24E-09,OR=2.23,95%CI=1.70-2.93)in CARD14 gene.?7 gene locis are associated with PsV,including rs118179173(P=2.30E-06,OR=2.32,95%CI=1.62-3.32),rs2247056(P=3.73E-04,OR=0.67,95%CI=0.53-0.83),rs3177928(P=1.37E-15,OR=2.51,95%CI=2.00-3.168)and HLA-Cw*06:02 in HLA gene;rs17728338(P=1.35E-04,OR=1.49,95%CI=1.21-1.83)and rs869976(P=9.74E-03,OR=1.72,95%CI=1.14-2.62)in TNIP1;rs3813063(P=1.21E-02,OR=1.18,95%CI=1.04-1.35)in CARD14 gene.?6 gene locis are related toGPP with PsV,including rs148755083(P=1.27E-34,OR=14.71,95%CI=8.51-25.44)in IL36RN;rs17728338(P=9.92E-08,OR=2.90,95%CI=1.93-4.37)in TNIP1 gene;HLA-Cw*06:02,rs118179173(P=1.16E-02,OR=2.49,95%CI=1.20-5.20),and rs3177928(P=6.38E-08,OR=3.30,95%CI=2.09-5.20)in HLA gene;rs3813063(P=6.48E-06,OR=2.22,95%CI=1.56-3.16)in CARD14 gene.?5 gene locis are related to GPP without PsV,including rs148755083(P=7.73E-103,OR=47.27,95%CI=5.16-105.70)and rs139497891(P=2.60E-09,OR=23.36,95%CI=5.16-105.70)in IL36RN gene;rs17728338(P=1.32E-13,OR=4.40,95%CI=2.88-6.72)inTNIP1gene,rs3813063(P=5.12E-05,OR=2.25,95%CI=1.51-3.36)in CARD14 gene and HLA-Cw*06:02in HAL gene.?In HLA-Cw*06:02 negative samples,6 gene mutations were still associated with GPP:rs118179173 and rs3177928 in HLA region,rs139497891 and rs148755083 in IL36RN region,rs17728338 in TNIP1 region and rs3813063 in CARD14 region.In HLA-Cw*06:02 positive samples,three gene mutations were associated with GPP:rs17728338 in TNIP1 gene region,rs3813063 in CARD14 gene region and rs148755083 in IL36RN gene region.In both HLA-Cw*06:02 positive and negative samples,three GPP-related gene mutations were rs17728338 in TNIP1 gene region,rs3813063 in CARD14gene region and rs148755083 in IL36RN gene region.Conclusion(1)HLA-Cw*06:02,HLA(rs3177928,rs118179173),IL36RN(rs139497891,rs148755083),CARD14(rs3813063),TNIP1(rs17728338)are correlated with GPP in the Han population of Inner Mongolia.(2)HLA-Cw*06:02,HLA(rs118179173,rs2247056,rs3177928),TNIP1(rs17728338?rs869976)and CARD14(rs3813063)are correlated with PsV in the Han population of Inner Mongolia.No correlation is found between AP1S3,CSMD1 genes and GPP.(3)Stratification analysis showed that in the Han population of Inner Mongolia,IL36RN(rs139497891)is correlated with GPP without PsV.HLA(rs118179173?rs3177928)is correlated with GPP with PsV.HLA-Cw*06:02,IL36RN(rs148755083),CARD14(rs3813063),TNIP1(rs17728338)are correlated with GPP with or without PsV.(5)HLA-Cw*06:02 stratified analysis showed that rs118179173(HLA),rs3177928(HLA)and rs139497891(IL36RN)are only associated with GPP in HLA-Cw*06:02 negative samples.In both negative and positive HLA-Cw*06:02 samples,the GPP-related loci were rs148755083in IL36RN,rs17728338 in TNIP1 and rs3813063 in CARD14.No single locus was associated with GPP in HLA-Cw*06:02 positive samples.