| Developmental dysplasia of the hip(DDH)is a major cause of osteoarthritis of hip joint common in young adults,it is associated factors including genetic,demography,internal secretion,breech presentation,primiparity,high birth weight,multiple pregnancy,polyhydramnios and tight swaddle.Within these factors,genetic factor is the most important factor.In molecular genetic studies of DDH,researchers had found most of the variation in regional or SNP located between genes and introns,possible regions associated with DDH are 13q22,17q21 and other regions,including PCHD9,HDAC5,MYST2,MPP3,FZD2,NSF,WNT3,HOXB2,IGF2BP1 genes,these data are analyzed in depth,and a large sample size SNP classification analysis is carried out for a variety of groups.The researchers conducted genome-wide association studies of the DDH core family to find some chromosomal regions or a variant of SNPs,and have successively proposed the gene families are associated with DDH,which are metalloproteinases,collagen,core glycan,growth factors,Homeobox gene and geometry related genes of the hip.In our study,we chose key genes expressd during limb development in Chinese Han population,mainly chose Tag SNPs in promoter regions and intron regions as research object,to investigate the association among genotype,allele frequency and haplotype of these genes and prevalence risk of DDH and different clinical phenotypes of DDH.And explain the influence of gene function by analysis difference between genotype,allele frequency,haplotype and protein level in plasma of patients and control group for prediction of prevalence risk of DDH,especially the risk of DDH core family menbers.Materials and methods1.In our study,we collected 123 sample of inpatient and outpatient of DDH patients in our hospital,and 261 sample of healthy control group,the samples are all peripheral blood,all the patients and healthy people samples were collected from China Han people,all samples performed with informed consent.2.We chose rs10983078(T/G),rs3810939(C/T),rs386088(G/A),rs405485(G/C),rs6478233(C/T),rs7020782(C/A),rs7847346(A/C),rs7875237(C/T)loci of PAPP-A gene;rs1040457(C/T),rs1044252(T/C),rs1883431(C/T),rs240097(G/A),rs41459046(C/G),rs4492574(C/T),rs742473(G/A)loci of PAPP-A2 gene;rs1048201(C/T),rs12644427(A/G),rs308401(A/G),rs308418(A/G),rs3747676(C/T)loci of FGF2 gene;rs1061237(A/G),rs2075555(C/A),rs2075559(C/G),rs2141279(C/T),rs2249492(T/C),rs2277632(A/G),rs2586488(G/A),rs2586494(C/A),rs2696247(A/G),rs748075(C/G)loci of COL1A1 gene.We chose a total of30 sites as the research object.We detect these loci through the Mass ARRAY technology and LDR technology,and use Shesis and SPSS for analysis of genotype,allele frequency,haplotype and protein expression level,the association between PAPP-A polymorphism and clinical phenotype,and the association of gene polymorphism,plasma protein levels with clinical phenotypes.Result1.Haplotype analysis of PAPP-A gene in T-C-A-G-C-C-A-C(p=0.015),T-T-AG-C-A-A-C(p<0.001),T-T-G-G-T-A-A-T(p=0.001)was significantly higher than the control group in the distribution of DDH in the case group;and T-T-A-G-C-C-A-C(p=0.046),T-T-G-G-C-A-A-T(p=0.022)was significantly lower than the control group in DDH patients;rs7847346 locus genotype has statistically significant in the range of involvement classification(p=0.002);rs7875237 locus genotype has statistically significant in Crown disease classification(p<0.001);the gene polymorphism of rs7020782 loci has statistically significant under recessive genetic model with Dunn classification(p=0.047);rs7847346 loci has statistically significant under dominant genetic model with the range of involvement classification(p=0.011);rs7875237 loci has statistically significant under additive genetic model and under recessive genetic model with gender classification(p<0.001).2.There are no statistically significant between DDH case group and control group in genotype,allele frequency,haplotype,plasma protein levels of 7 Tag SNPs of PAPP-A2 gene.Gene type of rs240097 loci has statistically significant with range of involvement classification in DDH group(p= 0.044);rs41459046 loci has statistically significant under dominant genetic m`odel with gender classification(p=0.050);genotypes of rs4492574 loci has statistically significant with plasma protein level of PAPP-A2;plasma protein level of PAPP-A2 has statistically significant with Dunn classification(p=0.018).3.There are no statistically significant between DDH case group and control group in genotype,allele frequency,haplotype,plasma protein levels of 5 Tag SNPs of FGF2 gene;rs1048201 loci has statistically significant with range of involvement classification in DDH group(p=0.039);rs12644427 loci has statistically significant under additive genetic model and under recessive genetic model with range of involvement classification(p=0.048).4.Genotype of rs2075555 loci has statistically significant between DDH group and control group(p=0.003);the expression of COL1A1 in plasma protein level has statistically significant between DDH group and control group(p=0.033);genotype of rs2075559 loci has statistically significant with Dunn classification(p=0.047);genotype of rs2586488 loci has statistically significant with Crown classification(p=0.043)and Dunn classification(p=0.047);rs1061237 loci(p=0.045)and rs2075559 loci(p=0.009)has statistically significant with Dunn classification under recessive genetic model;rs2141279 loci has statistically significant with Dunn classification under additive genetic model(p=0.018);rs2249492 loci has statistically significant with Crown classification(p=0.003)and Dunn classification(p=0.045)under recessive genetic model;rs2277632 loci has statistically significant with Dunn classification under recessive genetic model(p=0.047)and under recessive genetic model(p=0.030);rs2586488 loci has statistically significant with gender classificaion under overdominance genetic model(p=0.048).Conclusion1.The haplotype of the 8 Tag SNPs of PAPP-A gene(T-C-A-G-T-A-A-G,T-T-AG-C-A-A-C,T-T-A-G-C-C-A-C)is associated with the risk of DDH,rs2075555 loci of COL1A1 is associated with the risk of DDH.There is no relevance among the genetype,allele frequency of PAPP-A gene;the genetype,allele frequency and haplotype of PAPP-A2 gene and FGF2 gene;the allele frequency ad haplotype with the risk of DDH.2.Rs7020782 loci of PAPP-A gene has statistically significant with Dunn classification;rs7847346 loci has statistically significant under dominant genetic model with the range of involvement classification;rs7875237 locus genotype has statistically significant in Crown disease classification.Gene type of rs240097 loci has statistically significant with range of involvement classification in DDH group;rs41459046 loci has statistically significant under dominant genetic m`odel withgender classification.Rs1048201 loci of FGF2 gene has statistically significant with range of involvement classification in DDH group.Rs1061237 loci,rs2075559 loci,rs2141279 loci,rs2249492 loci,rs2277832 loci and rs2586488 loci of COL1A1 gene are associated with Dunn type;rs2249492 loci and rs2586488 loci are associated with Crown type.3.Genotypes of rs4492574 loci has statistically significant with plasma protein level of PAPP-A2;plasma protein level of PAPP-A2 has statistically significant with Dunn classification.The expression of COL1A1 in plasma protein level has statistically significant between DDH group and control group.The protein level in plasma of PAPP-A and FGF2 gene has no association with the risk of DDH and clinical types. |
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