Mediation roles of neutrophils and high-density lipoprotein (HDL) on the relationship between HLA-DQB1 and rosacea
Creators: name: Xiao, Wenqin
name: Li, Ji
name: Huang, Xin
name: Zhu, Quan
name: Liu, Tangxiele
name: Xie, Hongfu
name: Deng, Zhili
name: Tang, Yan
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Molecular Biology
subject: Ecology
subject: Immunology
subject: FOS: Clinical medicine
subject: Plant Biology
subject: Computational Biology

description: Though the previous genome-wide association studies found the association between <i>HLA</i> alleles and rosacea in the European populations, the data is lacking among the Asians. Moreover, neutrophils are important in the immune-related mechanism of rosacea, and dyslipidemia is closely related to rosacea. We aimed to explore the association between <i>HLA</i> genes and rosacea in Chinese rosacea patients, as well as the mediation effect of neutrophils, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) on the relationship between <i>HLA</i> genes and rosacea. A total of 249 rosacea and 150 controls were ranked by the international investigator global rosacea severity scores. <i>HLA</i> genes, neutrophils, HDL, and LDL were detected. And their mediation effects on the relationship between <i>HLA</i> and rosacea risk or severity were analysed. <i>HLA-DQB1*03:03</i> allele (OR = 41.89, 95% CI: 9.80 ∼ 179.09, <i>p</i> = 4.7*10<sup>−7</sup>), <i>HLA-DQB1*04:02</i> allele (OR = 0.16, 95% CI: 0.03 ∼ 0.81, <i>p</i> = 0.026) and <i>HLA-DQB1*03:03/05:02</i> genotype (OR = 5.57, 95% CI: 1.13 ∼ 27.52, <i>p</i> = 0.0351) were significantly associated with rosacea. Moreover, <i>HLA-DQB1*03:03</i> allele (b = 1.434, SE = 0.217, <i>p</i> = 2.0*10<sup>−10</sup>), <i>HLA-DQB1*05:01</i> allele (b = 0.894, SE = 0.33520, <i>p</i> = 0.008) and <i>HLA-DQB1*03:03/06:01</i> genotype (b = 0.998, SE = 0.472, <i>p</i> = 0.040) were positively associated with rosacea severity. Furthermore, we found both neutrophils and HDL, instead of LDL, have mediation effects on the relationship between <i>HLA-DQB1*03:03</i> and risk or severity of rosacea. We discovered novel susceptible <i>HLA</i> alleles for rosacea in the Chinese population, and disclosed the mediation effect of neutrophils and HDL on the relationship between <i>HLA-DQB1</i> and rosacea, implying a possible correlation between rosacea and inflammatory or metabolic factors, providing hints for future studies in the mechanism of rosacea.
Key messages<i>HLA-DQB1*03:03</i> allele, <i>HLA-DQB1*04:02</i> allele and <i>HLA-DQB1*03:03/05:02</i> genotype were significantly associated with rosacea.<i>HLA-DQB1*03:03</i> allele, <i>HLA-DQB1*05:01</i> allele and <i>HLA-DQB1*03:03/06:01</i> genotype were positively associated with rosacea severity.Neutrophils and HDL have mediation effects on the relationship between <i>HLA-DQB1*03:03</i> and risk or severity of rosacea. <i>HLA-DQB1*03:03</i> allele, <i>HLA-DQB1*04:02</i> allele and <i>HLA-DQB1*03:03/05:02</i> genotype were significantly associated with rosacea. <i>HLA-DQB1*03:03</i> allele, <i>HLA-DQB1*05:01</i> allele and <i>HLA-DQB1*03:03/06:01</i> genotype were positively associated with rosacea severity. Neutrophils and HDL have mediation effects on the relationship between <i>HLA-DQB1*03:03</i> and risk or severity of rosacea.