Mediation roles of neutrophils and high-density lipoprotein (HDL) on the relationship between HLA-DQB1 and rosacea.

ABSTRACT

BACKGROUND: Though the previous genome-wide association studies found the association between HLA 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 HLA 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 HLA genes and rosacea. METHODS: A total of 249 rosacea and 150 controls were ranked by the international investigator global rosacea severity scores. HLA genes, neutrophils, HDL, and LDL were detected. And their mediation effects on the relationship between HLA and rosacea risk or severity were analysed. RESULTS: HLA-DQB1*0303 allele (OR = 41.89, 95% CI 9.80 ∼ 179.09, p = 4.7*10-7), HLA-DQB1*0402 allele (OR = 0.16, 95% CI 0.03 ∼ 0.81, p = 0.026) and HLA-DQB1*0303/0502 genotype (OR = 5.57, 95% CI 1.13 ∼ 27.52, p = 0.0351) were significantly associated with rosacea. Moreover, HLA-DQB1*0303 allele (b = 1.434, SE = 0.217, p = 2.0*10-10), HLA-DQB1*0501 allele (b = 0.894, SE = 0.33520, p = 0.008) and HLA-DQB1*0303/0601 genotype (b = 0.998, SE = 0.472, p = 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 HLA-DQB1*0303 and risk or severity of rosacea. CONCLUSIONS: We discovered novel susceptible HLA alleles for rosacea in the Chinese population, and disclosed the mediation effect of neutrophils and HDL on the relationship between HLA-DQB1 and rosacea, implying a possible correlation between rosacea and inflammatory or metabolic factors, providing hints for future studies in the mechanism of rosacea. Key messagesHLA-DQB1*0303 allele, HLA-DQB1*0402 allele and HLA-DQB1*0303/0502 genotype were significantly associated with rosacea.HLA-DQB1*0303 allele, HLA-DQB1*0501 allele and HLA-DQB1*0303/0601 genotype were positively associated with rosacea severity.Neutrophils and HDL have mediation effects on the relationship between HLA-DQB1*0303 and risk or severity of rosacea.