Yin Xiangli, Zhu Quan, Li Ji, Zou Yizhou, Luo Qizhi
Department of Immunology, Xiangya School of Basic Medical Sciences, Central South University, Changsha 410013.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Mar 28;50(3):319-330. doi: 10.11817/j.issn.1672-7347.2025.240531.
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.
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.
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.
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.
主要组织相容性复合体I类链相关基因A（MICA）是人类白细胞抗原（HLA）基因复合体的一个组成部分，参与包括癌症和自身免疫性疾病在内的多种疾病的发病机制。酒渣鼻是一种发病机制复杂的慢性炎症性皮肤病，可能受遗传和自身免疫因素影响。本研究旨在探讨MICA基因多态性、单核苷酸多态性（SNP）与酒渣鼻易感性之间的关系，从而为该疾病的发病机制提供新的见解。
收集2017年11月至2019年11月期间到中南大学湘雅医院皮肤科门诊就诊的84例酒渣鼻患者（酒渣鼻组）和223名健康志愿者（对照组）的外周血DNA样本。采用基于聚合酶链反应测序的分型（PCR-SBT）和下一代测序（NGS）进行MICA基因分型，并比较两种方法的准确性。分析两组之间MICA等位基因的频率分布。进行氨基酸聚类和SNP位点分析，以鉴定单倍型相关的SNP，并对MICA多态性变体进行分类。还检查了两组之间这些分类的分布差异。
酒渣鼻患者的血液检查显示轻度升高，淋巴细胞计数无明显变化。PCR-SBT和NGS均准确鉴定出MICA等位基因。酒渣鼻组中最常见的等位基因是A4、A5和A6。与对照组相比，酒渣鼻组中A4和A5的频率显著降低（分别为6.55%对18.16%和1.19%对5.38%），而A6和A9的频率显著升高（分别为7.74%对3.36%和31.55%对18.61%；均P<0.05）。鉴定出5个短串联重复（STR）等位基因。酒渣鼻组中A4和A5的频率低于对照组（分别为16.07%对23.32%和7.74%对17.26%），而A6的频率较高（10.12%对4.03%；均P<0.05）。聚类和SNP分析鉴定出6个连锁SNP位点，将MICA变体分为I型（C+M+K+G+W+S）和II型（Y+V+E+S+R+T）。I型MICA变体与酒渣鼻易感性显著相关。
MICA基因多态性与酒渣鼻易感性相关，且MICA基因内存在6个连锁SNP位点。据此，MICA多态性变体分为I型和II型，其中I型与酒渣鼻的疾病发展关系更为密切。
