| Objective:To discussion association of FOXP3 single nucleotide polymorphisms(SNPs)with susceptibility to alopecia areata of GuiZhou Han Population.Methods:250 alopecia areata patients and 200 normal controls in Guizhou Han population were collected as research objects.The genotypes of four SNPs of FOXP3(rs3761547,rs3761548,rs3761549,rs2232365)in all the objects were detected by SNaPshot technique.SPSS 20.0 statistical software was used for statistical analysis of experimental data.The χ2 test was used to analyze the differences in genotype and allele frequencies between the two groups,and non-conditional logistic regression analysis was used to analyze its association with alopecia areata.The χ2 test was used to test whether the FOXP3 gene was consistent with the Hardy-Weinberg equilibrium(HWE)and to determine the population representativeness of the study subjects.Link disequilibrium and haplotype analysis were performed using SHEsis online software.Results:1.HWE test showed that the frequency of genotypes of four SNPs(rs3761547,rs3761548,rs3761549,rs2232365)of FOXP3 gene all reached the genetic balance in the normal control group(rs3761547:χ2=0.780,P=0.377;rs3761548:χ2=0.175,P=0.675;rs3761549:χ2=1.179,P=0.278;rs2232365:χ2=3.561,P=0.059).2.There was A>G mutation in rs3761547 of FOXP3 gene,which resulted in GG,AG and AA genotypes.The genotype GG and allele G,A frequency were statistic significantly different between the groups of alopecia areata and normal control(P<0.001,P=0.002).There were significant differences in the distribution between the two groups in the recessive mode[GG vs(AG +AA)],overdominant mode[(GG + AA)vs AG]and accumulation mode[GG vs AG vs AA](P<0.001,P=0.041,P<0.001),the distribution differences in dominant mode[(AG + GG)vs AA]were not statistically significant(P=0.294).Genotype GG,allele G,recessive mode[GG vs(AG + A A)]and overdominant mode[(GG + AA)vs AG]were all risk factors for alopecia areata,whereas dominant pattern[GG vs AG vs AA]was not associated with alopecia areata.The distribution of genotype and allele frequencies of this locus in male and female cases of alopecia areata was significantly different(P<0.001),and allele A may be a protective factor to male alopecia areata patients.There was no significant differences in the distribution of first onset age,course of disease,recurrence,activity,family history and type of hair loss in alopecia areata cases(P>0.05).There exists C>A mutation in rs3761548 of FOXP3 gene,which results in AA,AC and CC genotypes.The genotype AA and allele A,C were significantly different between the groups of alopecia areata and normal control(P<0.001,P=0.001).There were significant differences in the distribution between the two groups in the recessive mode[AA vs(AC+CC)],accumulation mode[AA vs AC vs CC](P<0.001),the distribution differences in dominant mode[(AC+AA)vs CC],overdominant mode[(AA+CC)vs AC]were not statistically significant(P=0.204,P=0.121).Genotype AA,allele A,recessive mode[AA vs(AC+CC)]were all risk factors for alopecia areata,while dominant pattern[(AC+AA)vs CC]and overdominant mode[(AA+CC)vs AC]were not associated with alopecia areata.The distribution of genotypes of this locus in male and female patients of alopecia areata was significantly different(P<0.001).There was no significant differences in the distribution of first onset age,course of disease,recurrence,activity,family history and type of hair loss(P>0.05).There was no significant difference in the distribution of allele frequency in all clinical phenotypes of alopecia areata(P>0.05).There was C>T mutation in rs3761549 of FOXP3 gene,which showed TT,CT and CC genotypes.The genotype TT and allele T,C frequencies were significantly different between the groups of alopecia areata and normal control(P<0.001,P= 0.001).There were significant differences in the distribution between the two groups in the recessive mode[TT vs(CT+CC)],overdominant mode[TT vs CT vs CC](P<0.001),the distribution differences in dominant mode[(CT+TT)vs CC]and overdominant mode[(TT+CC)vs CT]were not statistically significant(P=0.222,P=0.079).Genotype TT,allele T and recessive mode[TT vs(CT+CC)]were all risk factors for alopecia areata,while dominant pattern[(CT+TT)vs CC]and overdominant mode[(TT+CC)vs CT]were not associated with alopecia areata.The distribution of allele frequencies of this locus in first onset age cases of alopecia areata was significantly different(P=0.049),and allele C may be a protective factor to the alopecia areata patients whose first onset of age was younger than 30 years old There was no significant difference in the distribution of gender,course of disease,recurrence,activity,family history and type of hair loss(P>0.05).There was no significant difference in the distribution of genotype frequencies in all clinical phenotypes of alopecia areata(P>0.05).There was A>G mutation in rs2232365 of FOXP3 gene,including GG,AG and AA genotypes.The genotype GG and allele G,A frequencies were significantly different between the groups of alopecia areata and normal control(P<0.001).There were significant differences in the distribution between the two groups in the recessive mode[GG vs(AG+AA)],dominant mode[(AG+GG)vs AA],overdominant mode[(GG+AA)vs AG]and accumulation mode[GG vs AG vs AA](P<0.001,P=0.043,P=0.003,P<0.001).Genotype GG,allele G,recessive mode[GG vs(AG+AA)],dominant mode[(AG+GG)vs AA]and overdominant mode[(GG+AA)vs AG]were all risk factors for alopecia areata.The distribution of genotype frequencies of this locus in male and female patients of alopecia areata was significantly different(P<0.001).There was no significant differences in the distribution of first onset age,course of disease,recurrence,activity,family history and type of hair loss(P>0.05).There was no significant difference in the distribution of alleles in all clinical phenotypes(P>0.05).3.Linkage disequilibrium analysis:In alopecia areata group,there is strong linkage disequilibrium between rs3761547 and rs3761548(D’=0.999,r2=0.047),rs3761547 and rs2232365(D’=0.981,r2=0.350),rs3761548 and rs2232365(D’=0.964,r2=0.383).There is linkage disequilibrium between rs3761548 and rs3761549(D’=0.302,r2=0.004)while,there is no linkage disequilibriumbetween rs3761547 and rs3761549(D’=0.014,r2=0),rs3761549 and rs2232365(D’=0.093,r2=0.001).In normal control group,there is complete linkage disequilibrium between rs3761547 and rs3761549(D’=1.000,r2=0.943),rs3761547 and rs2232365(D’=1.000,r2=0.413),rs3761548 and rs2232365(D’=1.000,r2=0.472),rs3761549 and rs2232365(D’=1.000,r2=0.389).There is strong linkage disequilibrium between rs3761548 and rs3761549(D’=0.677,r2=0.006),and linkage disequilibrium between rs3761547 and rs3761548(D’=0.479,r2=0.003)in linkage disequilibrium.In alopecia areata group and normal control group,there is strong linkage disequilibrium between rs3761547 and rs3761548(D’=O.997,r2=0.029),rs3761547 and rs2232365(D’=0.988,r2=0.378),rs3761548 and rs2232365(D’=0.978,r2=0.419).There is linkage disequilibrium between rs3761547 and rs3761549(D’=0.318,r2=0.097),rs3761548 and rs3761549(D’=0.273,r2=0.002),rs3761549 and rs2232365(D’=0.296,r2=0.033).4.Haplotype analysis:Four SNPs(rs3761547,rs3761548,rs3761549,rs2232365)of FOXP3 gene can construct ten kinds of haplotypes(ACCA,AACG,GCCG,GCTG,AACA,AATG,ACCG,ACTA,ACTG,GCC A).The distribution of AACG,ACC A,GCCG,GCTG and ACTA haplotype frequencies in alopecia areata group and normal control group were significantly different(P<0.05).Haplotype AACG and GCCG are risk factors for alopecia areata,haplotype ACCA and GCTG are protective factors of alopecia areata.It is predicted that the risk of developing alopecia areata with G,A and T alleles will increase.The G,A and T alleles were risk factors for the development of alopecia areata in Guizhou Han;There was linkage disequilibrium among FOXP3 gene rs3761547,rs3761548,rs3761549,rs2232365 single nucleotide polymorphisms.The haplotypes AACG and GCCG may be risk factors for the development of alopecia areata in Guizhou Han population.Haplotype ACCA and GCTG may be the protective factors of Guizhou Han alopecia areata.The four sites of FOXP3 gene SNPs were correlated with common clinical phenotypes of Guizhou Han alopecia areata for the first time.Conclusion:1.FOXP3 gene rs3761547,rs3761548,rs3761549,rs2232365 may be related to the susceptibility of alopecia areata in Guizhou Han population.In FOXP3 gene,the G allele of rs3761547 and rs2232365,the A allele in rs3761548,and the T allele in rs3761549 all increased the risk of Han alopecia areata in Guizhou.The risk of developing alopecia areata in men with the A allele at rs3761547 is predicted to decrease.The A allele was a protective factor for alopecia areata in Guizhou Han males.The rs3761549 locus carrying the C allele will reduce the risk of developing alopecia areata in patients younger than 30 years of age.The C allele is a protective factor for patients with alopecia areata in Guizhou Han of age less than 30 years.The FOXP3 gene polymorphism may play a different role in different clinical phenotypes. |
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