| Refractive error is the leading cause of low vision worldwide,and the second leading cause of low vision in Yunnan province.It is an important public health issue.School age is the most common age forthe occurrence and development of refractive errors,especially myopia.In recent years,the prevalence of myopia is increasing.The exact cause of myopia is remain unclear.The differences in the composition and the prevalence of refractive error may be caused by genetic and environmental factors,however there is no conclusion which factors play a leading role.Mojiang county is located in the Southern Yunnan,and majority of local population are ethnic minorities(mostly Hani people).Up to now,no relevant genetic study on myopiain this region has been published.This study is aimed to explore the preliminary role of genetic factors in Hani juvenile myopia,and provide clues for the future genetic studies on myopia in Hani people.Objective:Based on results from previous genetic studies and animal,laminina chain,gap junction protein delta 2,tubulin family,Ras protein-specific guaninenucleotide-releasing factorl,catenin delta 2,Transforming growth factor-beta,bonemorphogenic protein were chosen as candidate genes.The purpose of this study is to explore the influence factors of genetic factors in the occurence and development of myopia and to provide clues for exploring the molecular genetic mechanism of myopia in Hanipeople.Methods:TGF-p,BMP,LAMA1,GJD2,CTNND2,RASGRF1 and TUBA were selected as candidate genes.Open the NCBI-SNP(http://www.ncbi.nlm.nih.gov/snp/)website,screening of functional site requirements preliminary.Minor allele frequency was asked for greater than 0.2(MAF>0.2).We accessed to relevant literature and disease susceptibility results were marked.Then we worked on the punctional prediction of primary loci.Ultimately determined the 30 SNP loci of selected candidate genes:TGF-?1(rs1800469,rs1800472,rs2241716,rs4803455),TGF-?2(rsl473527,rs6604604,rs6691070,rs7550232,rs900),BMP-2(rs173107,rs235768,rs4813802,rs961253,rs235770),BMP-3(rs13138361,rs1390319,rs1960445,rs3733549,rs4458448,rs5022942),BMP-4(rs17563,rs2761887,rs4901474,rs66913363),LAMA1(rs12205363),GJD2(rs524952),CTNND2(rs6885224?rs12716080),RASGRF1(rs4778879),TUBA(rs10034228).In the urban area of Mojiang County in Yunnan province,12-18 years old middle school students based on the screening of myopic students.Totally 67 Hanimyopic students were recruited.Written consent was given by the students'guardians after fully explaination of the purpose and process of the study.A blood sample of 5ml was extracted from elbow vein for DNA extraction.The single nucleotide polymorphisms of 30 candidate genes were analyzed by Sequenom.Log.From the 1000Genomes database,looking for nomal Chinese people genes which are totally 103 dataes were used as controls for candidate gene loci.IBM SPSS 20.0 was used to analyze the data by Pearson chi square test or Fisher exact test,to analyze the differences of genotype and allele frequencies between normal and disease groups at each locus,and to search for disease related loci.Haploview4.2 software was used to analyze the linkage disequilibrium and haplotype based on linkage disequilibrium in 7 SNPs,and the results were analyzed by permutation test.Results:1)The 30 loci,BMP-2(rs235768)was not detected,and the remaining 29 loci detection rate was>90%.2)statistical analysis of genotype distribution in 3 polymorphic loci TGF-?1(rs2241716),BMP4(rs66913363),CTNND2(rs6885224)gene in dominant genetic model and control group distribution compared with statistical difference(P = 0,0.007,0.023);and in the recessive under the mode of only two polymorphic loci BMP4(rs4901474,rs66913363)and control group,the genotype distribution difference was statistically significant(P = 0.030,0);the rest have no significant difference between the two groups.In the statistical analysis of gene frequencies in 2 polymorphic loci TGF-?1(rs2241716),BMP4(rs66913363)in the control group with statistical difference(P =<0.05),the rest of the points statistics has no difference.3)Three locis of TBG-?1 gene defines a block,rs1800469 and rs2441716 weak linkage disequilibrium(D=0.97,r2=0.33),four locis of BMP4 defines a block,rs66913363 and rs 17563 weak linkage disequilibrium(D=0.97,r2=0.52).The BMP4's haplotype of CG and TG two in myopia group and control group was statistically significant(P = 3.74E-05,1.00E-09);TBG-?1's haplotypes CG,GG two in myopia group and control group was statistically significant(P =5.16E-13,4.12E-15).Conclusion:Four sites are detected to be related to the occurrence and development of myopia in Mojiang Hani teenagers,including CTNND2(rs6885224),TGF-?1(rs2241716),BMP4(rs66913363,rs4901474). |
PDF Full Text Request