Association of gene polymorphisms and SNP loci with susceptibility to rosacea.

Objectives: The major histocompatibility complex class I chain-related gene A (), a component of the human leukocyte antigen () gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism.

Methods: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined.

Results: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified alleles. The most common alleles in the rosacea group were , , and . The frequencies of and were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all <0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of and were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas was higher (10.12% vs 4.03%; all <0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C+M+K+G+W+S) and Type II (Y+V+E+S+R+T). Type I MICA variants were significantly associated with rosacea susceptibility.

Conclusions: gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.