Study On The Association Between MICA Polymorphism And Rosacea Disease In Hunan Han’s Population

Rosacea is a chronic inflammatory skin disease that occurs in the middle of the face,mainly involving the facial blood vessels and the peripheral units of the hair follicles and sebaceous glands.It is characterized by skin flushing,erythema,papule,pustule,telangiectasia,etc...Rosacea and some autoimmune diseases(such as type 1 diabetes mellitus T1DM,celiac disease(CD),multiple sclerosis,and rheumatoid arthritis)are genetically related to individuals.Previous studies revealed that HLA-DRB1*03:01,HLA-DQB1*02:01,HLA-DQA1*05:01,and the single-nucleotide polymorphisms(SNPs)of HLA–DRA and butyrophilin-like 2(BTNL2)genes were associated with genetic susceptibility to rosacea disease.Additionally,non-genetic factors such as cigarette smoking,alcohol consumption,hot baths,ultraviolet(UV)radiation,Demodex folliculorum,emotional stress,hot weather,wind,heavy exercise,cold weather,spicy foods,etc.…are related to rosacea onset.Objective:The main purpose of this study is to analyze whether MICA gene polymorphisms are associated with rosacea disease in Han Chinese from Hunan province,southern China.Methods:Eighty-four(84)patients with rosacea disease and two hundred and twenty-three(223)healthy volunteers were recruited from the Department of Dermatology,Xiangya hospital.Three(3)ml of anticoagulated peripheral blood was collected.Then,genomic DNA was extracted from venous blood samples of all subjects by the standard salting-out method recommended by the World Health Organization,and high-resolution DNA genotyping of the MICA gene was performed using PCR-SBT(Sanger Sequence-Base-Typing).Statistical analysis of each MICA allele frequency was performed using the chi-square test.In addition,Bonferroni’s correction assessed two-sided probability P-values;P<0.05 was considered statistically significant.Results:We typed MICA genotypes in 84 rosacea patients and 223 healthy individuals.Fourteen(14)MICA alleles and 5 MICA-TM alleles(STR Typing)were detected.Among them,four(4)MICA alleles,MICA*002:01,MICA*009:01,MICA*010:01,and MICA*027,have obvious differences in the distribution frequencies of rosacea patients and healthy control.Decreased allele frequencies of MICA*002:01 and MICA*027 were observed in rosacea patients when compared with normal subjects(6.5%vs.16.77;χ~2=8.81,P<0.05);(1.2%vs.4.97%;χ20.02,P=0.02<0.05).This was associated with a corresponding increased allele frequency of MICA*009:01 and MICA*010:01 in the rosacea patient compared with the healthy control groups(7.7%vs.3.11%;χ~2=4.94,P=0.02<0.05);(31.5%vs.17.18%;χ~2=8.78,P<0.05).At the same time,we analyzed the transmembrane type(TM type)of the MICA gene using PCR-SBT software.We found that the frequency of MICA-A4 and MICA-A9 in rosacea patients was significantly lower than in normal subjects(16.1%vs.23.3%;P=0.03<0.05);(7.7%vs.17.3%;P<0.05).In contrast,the frequency of MICA-A6 in rosacea patients was significantly higher than in normal subjects(10.1%vs.4%;P<0.001).The Hardy-Weinberg test was carried out on all the research subjects.All the subjects were in line with the Hardy-Weinberg equilibrium,indicating that the research sample conformed to the principle of random sampling and was representative of the group.Conclusion:These results indicate that MICA*009:01 and MICA*010:01 may have a certain positive correlation with the pathogenesis of rosacea.In contrast,MICA*002:01 and MICA*027 may negatively correlate with rosacea.At the same time,we performed STR typing on the transmembrane region type(TM type)of the MICA gene using SBT software.We found that the frequency of MICA-A4 and MICA-A9 in rosacea patients was significantly lower than in normal people suggesting that MICA-A4 and MICA-A9 alleles may negatively correlate with the pathogenesis of rosacea.In contrast,the frequency of MICA-A6 was considerably higher in rosacea patients than in normal people,confirming that MICA-A6 may have a positive correlation with rosacea onset.