线粒体DNA控制区变异与瘢痕疙瘩的相关性研究

目的:探讨线粒体DNA（mtDNA）控制区D环（D-loop）的突变与瘢痕疙瘩的相关性。方法:收集2016—2019年昆明医科大学第一附属医院皮肤科门诊瘢痕疙瘩患者216例，提取患者外周血总DNA及25例患者的瘢痕疙瘩组织、瘢痕疙瘩旁正常组织的总DNA。以云南大学附属医院体检中心无瘢痕疙瘩的健康体检者299例外周血样本...

Correlation between mitochondrial DNA control region variations and keloid formation

【Abstract】 Objective To investigate the correlation between variations in mitochondrial DNA （mtDNA） control region （D-loop） and keloids. Methods A total of 216 patients with keloids were collected from Department of Dermatology, the First Affiliated Hospital of Kunming Medical University from 2016 to 2019. Total DNA was extracted from peripheral blood samples of all the patients, as well as keloid tissues and perilesional normal skin tissues of 25 patients with keloids. Peripheral blood samples were collected from 299 health checkup examinees without keloids in Health Examination Center, the Affiliated Hospital of Yunnan University, who served as controls. PCR amplification and Sanger sequencing were performed on the mtDNA D-loop region, and mutation sites in each sample were analyzed by comparisons with the revised Cambridge Reference Sequence （rCRS）. Haplogroups were assigned in the 2 groups by using Phylotree-mtDNA tree Build 17. Mutations in the mtDNA D-loop region were compared among keloid tissues, perilesional normal skin tissues and peripheral blood samples. A median-joining network was constructed via network 5.0 software. Binary logistic regression analysis was performed to investigate the correlation between haplogroup frequencies and the occurrence of keloids, and chi-square, t and t′ tests were used to analyze clinical data. Results Among the 216 patients with keloids, variations in mtDNA D-loop region were classified into 10 haplogroups, including A, B, D, R9, G, M*, M7, M8, M9 and N9, with the haplogroups R9 and M9 showing the highest （21.3%, 46/216） and lowest （0.9%, 2/216） frequencies respectively. The frequencies of haplogroups M7 （P = 0.040, OR = 0.248, 95% CI: 0.066 - 0.937） and N9 （P = 0.048, OR = 0.191, 95% CI: 0.037 - 0.986） were significantly lower in the patients with keloids than in the controls. The median-joining network plot showed that the distribution pattern of the haplogroup M7 differed between the patients with keloids and controls. Significantly less number of lesional sites and younger age of onset were observed in the patients with haplogroup M7 compared with those with non-M7 haplogroups （P = 0.000 1, 0.045, respectively）. Conclusion The haplogroup M7 is correlated with the occurrence of keloids, and may be a potential protective factor for keloid formation.