关键词: 银屑病, 白细胞介素12, 遗传关联研究, 多态性, 单核苷酸, 汉族, 蒙古族, HLA抗原, HLA-Cw*0602, 交互作用

Abstract: 【Abstract】 Objective To investigate the genetic correlation of interleukin-12 （IL-12） pathway-related gene single nucleotide polymorphisms （SNPs） with psoriasis vulgaris and their interaction with HLA-Cw*0602 in populations of Mongolian and Han nationalities in Inner Mongolia. Methods From December 2012 to March 2018, 1 409 inpatients with psoriasis vulgaris （1 030 of Han nationality and 379 of Mongo-lian nationality） and 1 483 healthy controls （965 of Han nationality and 518 of Mongolian nationality） were collected from the Affiliated Hospital of Inner Mongolia Medical University, and served as patient group and control group respectively. Five milliliters of peripheral venous blood samples were collected from these subjects, and DNA was extracted. Nine SNPs located in the coding regions of IL-12 pathway-related genes were selected, including IL-12B （rs2082412, rs2288831, rs3212227, rs3213094, rs7709212）, IL-23R （rs11209026, rs2201841, rs7530511） and IL-28RA （rs4649203） genes, and detected by next-generation sequencing. HLA-Cw*0602 was genotyped by polymerase chain reaction with sequence-specific primers （PCR-SSP）. Statistical analysis was carried out with PLINK1.07 software, Chi-square test was used to compare allele frequencies between the 2 groups, relative risk estimates of alleles were calculated by using odds ratio （OR）, and chi-square test for R × C contingency tables was used for haplotype analysis. Results The allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in the patients with psoriasis vulgaris of Han nationality than in the controls of Han nationality （all P < 0.005）; the allele frequency of rs3213094 in the IL-12B gene was significantly lower in the patients of Mongolian nationality than in the controls of Mongolian nationality （P < 0.005）. The prevalence of HLA-Cw*0602 was significantly lower in the patients with psoriasis vulgaris of Han and Mongolian nationalities than in the controls of corresponding nationalities （both P < 0.005）. As stratification analysis showed, the allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in HLA-Cw*0602-positive patients of Han nationality than in HLA-Cw*0602-positive controls of Han nationality （all P < 0.005）, while there was no significant difference between HLA-Cw*0602-negative patients of Han nationality and HLA-Cw*0602-negative controls of Han nationality （all P > 0.05）. Among the HLA-Cw*0602-positive or negative populations of Mongolian nationality, no significant difference was observed in the allele frequencies between the patients and controls （all P > 0.005）. Haplotypes were constructed using 5 SNPs in the IL-12B gene, and there was no significant difference in the frequencies of 6 haplotypes between the patients and controls of Mongolian or Han nationality （all P > 0.005）; stratification analysis showed that there was no significant difference in the frequencies of 7 haplotypes between HLA-Cw*0602-positive/negative patients and controls of Mongolian or Han nationality （all P > 0.005）. Conclusion IL-12 pathway-related gene polymorphisms are associated with psoriasis vulgaris in the populations of Mongolian and Han nationalities in Inner Mongolia, and there may be interaction between IL-12B and HLA-Cw*0602 in the occurrence of psoriasis vulgaris.

Key words: Psoriasis, Interleukin-12, Genetic association studies, Polymorphism, single nucleotide, Han nationality, Mongolian nationality, HLA antigens, HLA-Cw*0602, Correlation analysis