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

Wenqin Xiao; Ji Li; Xin Huang; Quan Zhu; Tangxiele Liu; Hongfu Xie; Zhili Deng; Yan Tang

doi:10.1080/07853890.2022.2077427

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

Ann Med. 2022 Dec;54(1):1530-1537. doi: 10.1080/07853890.2022.2077427.

Authors

Wenqin Xiao^{1

2

3

4}, Ji Li^{1

2

3

4}, Xin Huang⁵, Quan Zhu⁶, Tangxiele Liu^{1

2

3

4}, Hongfu Xie^{1

2

3

4}, Zhili Deng^{1

2

3

4}, Yan Tang^{1

2

3

4}

Affiliations

¹ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
² Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁴ Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South Univerisity, Changsha, China.
⁵ Department of Epidemiology and Biostatistics, School of Medicine, Hunan Normal University, Changsha, China.
⁶ Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

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*03:03 allele (OR = 41.89, 95% CI: 9.80 ∼ 179.09, p = 4.7*10^-7), HLA-DQB1*04:02 allele (OR = 0.16, 95% CI: 0.03 ∼ 0.81, p = 0.026) and HLA-DQB1*03:03/05:02 genotype (OR = 5.57, 95% CI: 1.13 ∼ 27.52, p = 0.0351) were significantly associated with rosacea. Moreover, HLA-DQB1*03:03 allele (b = 1.434, SE = 0.217, p = 2.0*10^-10), HLA-DQB1*05:01 allele (b = 0.894, SE = 0.33520, p = 0.008) and HLA-DQB1*03:03/06:01 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*03:03 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*03:03 allele, HLA-DQB1*04:02 allele and HLA-DQB1*03:03/05:02 genotype were significantly associated with rosacea.HLA-DQB1*03:03 allele, HLA-DQB1*05:01 allele and HLA-DQB1*03:03/06:01 genotype were positively associated with rosacea severity.Neutrophils and HDL have mediation effects on the relationship between HLA-DQB1*03:03 and risk or severity of rosacea.

Keywords: HLA; Rosacea; high-density lipoprotein; neutrophil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
HLA-DQ beta-Chains
Humans
Lipoproteins, HDL* / genetics
Neutrophils
Rosacea* / genetics

Substances

HLA-DQ beta-Chains
HLA-DQB1 antigen
Lipoproteins, HDL

Grants and funding

This research was supported by grants from the National Natural Science Foundation of China [NSFC; 82073467, 81874251, 81974480, 82073457].