Association Study Between NEDD4,DUSP10 Genes And Keloid In Han Population

Introduction Keloids is a unique pathological healing phenomenon,which is caused by abnormal hyperplasia of collagen fibers after skin injury.It is a frequently occurring disease in the field of dermatology.Keloids usually occur after the healing of skin injury,showing hyperplastic dense fibrous tissue,beyond the scope of the original injury,can not subside,can be accompanied by varying degrees of itching and pain,and easy to relapse after resection.Keloid is most common in the sternal region,patients with local pain and itching is obvious,in addition to the quality of life has a significant impact,and even has a great impact on the mental health of patients,secondary to burns,severe patients with scald can affect the affected limb function,bring a heavy burden to the family and society.With the increasing development of social economy,keloid is more and more concerned by the medical community,and the majority of patients urgently need effective treatment.Epidemiological investigation showed that the incidence rate of keloids was 4.5% to 16%,and the incidence of colored race was significantly higher than that of white race.Genetic epidemiological studies showed that the heritability of the first degree relatives of keloid patients were 72.45% respectively,suggesting that genetic factors played a major role in the pathogenesis of keloid.In the early stage,family linkage analysis showed that chromosome 2q23,7p11 and 18q21.1 were associated with keloid susceptibility,and the genetic model was autosomal dominant inheritance.In 2014,Japanese scholars found SNP rs8032158 site related to keloid,which is located in the intron region of NEDD4 gene.Domestic scholars have also carried out a study on the correlation of keloid in Chinese Han population.SNP rs2271289 in the intron region of NEDD4 gene was found to be associated with Chinese Han population.The SNPs that have been found to be related to the pathogenesis of keloid are located in the intron region of the gene,which can not explain the effect of gene function.The SNP mutation in NEDD4 promoter region has been confirmed to be associated with the disease.The completed studies on keloid in Han nationality have found that there is a potential susceptibility signal of keloid near DUSP10 gene,but there is no significant association in European population.Therefore,DUSP10 gene may be a susceptibility gene of keloid in Han nationality.Searching for the correlation between NEDD4 gene and DUSP10 gene and keloid is of great clinical significance to find an effective target for the treatment of keloid and to provide a new idea for overcoming this refractory skin disease.Objective Through the analysis of the gene data of keloid patients and normal control samples,we further explored whether the genetic variation of NEDD4 gene promoter region and DUSP10 gene were correlated with keloid susceptibility in Chinese Han population.Methods Four SNPs（rs873549,rs10518830,rs4774833,rs1781930）in NEDD4 and DUSP10 were included in the study.Genotyping was performed using Sequenom Massarray technology platform.The study population included 387 keloid patients in the case group and 1172 healthy persons in the control group,all of whom were Han people.The genotyping results were analyzed by PLINK 1.07 software,and the distribution of rs873549,rs10518830,rs4774833,and rs1781930 gene frequencies between case and control were calculated.Results Three SNPs showed no significance in the verified population（P >0.05）,（rs1051883:OR=1.379,P=0.6367;rs4774833: OR =1.016,P = 0.8854;rs1781930:OR = 0.9576,P = 0.6801）.There was a statistical difference in one SNP locus（P<0.05）（rs873549: OR=1.379,P=0.002688）.Among them,rs10518830,rs4774833 and rs1781930 are located on NEDD4 gene,and rs873549 is located near DUSP10 gene.Conclusions The results showed that the promoter region of NEDD4 gene rs10518830,rs4774833 and rs1781930 had no significant correlation with keloid,and it was again confirmed that the potential SNPs site near DUSP10 gene（rs873549）was correlated with keloid in Chinese Han people,and DUSP10 gene may be a keloid susceptibility gene in Chinese people.