| Objective:From the perspective of genetic,discusses the han population in north China IL-4(rs8179190)and ALDM1A2(rs3204689)gene polymorphism and knee joint osteoarthritis(KOA)and the relationship between the severity of disease.Osteoarthritis(OA)is caused by joint pain and dysfunction the most common diseases,that has become the world's fourth largest disabling disease.OA has proven to be a regulated by many factors of genetic disease.Interleukin-4(interleukin-4,IL-4)is an important anti-inflammatory cytokines,and its content was significantly higher in osteoarthritis synovial fluid.Studies have shown that IL-4 gene intron 3 variable repeat polymorphism may affect the expression of IL-4 gene,which affects the incidence of osteoarthritis of the knee.Aldehyde dehydrogenase 1 family member A2 is a key enzyme,which catalyzes the oxidation of retinal to retinoic acid.Retinoic acid and its receptor can regulate gene expression,and then regulate cell growth and differentiation.Foreign studies have shown that ALDH1A2 gene and severe hand osteoarthritis obviously related.But at present domestic,there is no literature reports about and the relationship between IL-4 and ALDM1A2 gene polymorphisms with severe knee osteoarthritis.This study will help to locate KOA susceptibility genes,it is expected to provide an important basis for the high-risk groups of knee osteoarthritis screening,early prevention,drug research and development KOA gene chips.Methods: using population-based case-control study method,collecting 189 cases of KOA as case group and 195 cases of patients with relatively healthy individuals as control group,in the case of patients' informed consent,collecting venous blood 1 ml each object of study,and records the history and related personal information.Genome TIANamp blood extraction kit was used to extract,collecting specimens of blood leukocyte DNA,the polymerase chain reaction-ligase detection reaction method and polymerase chain reaction-restriction fragment length polymorphism detection method,detection IL-4(rs8179190)and ALDH1A2(rs3204689)gene polymorphism loci of genotype and allele frequency distribution.Version data statistical analysis using SPSS13.0 software package(SPSS Company in New York,Chicago,Illinois,USA),P < 0.05 that was statistically significant.For each gene loci of genotype and allele frequency distribution,Hardy-Weinberg equilibrium analysis.Of case group and the control of the distribution of genotype and allele frequency comparison using the list line by chi-square test.Will KOA patients according to Kellgren-Lawrence(K/L)different grouping classification,using the chi-square test cases each genotype frequency distribution is analyzed in different groups.According to Body Mass Index(BMI)and the age stratification analysis of all the research object,using the chi-square test comparing genotypes have obvious difference in the individual stratification.With unconditional Logistic regression method to calculate by gender,age,BMI,correction of the ratio of the relative risk degree odds thewire(OR)and 95% confidence interval(the confidence interval,CI).Results:1 All the genotype frequency distributions of the three IL-4(rs8179190)and ALDH1A2(rs4746720)in our control subjects followed Hardy-Weinberg equilibrium proportions.2 The frequency of BMI?28kg/m~2 patients was significantly higher than that in healthy controls(?~2=5.014,P=0.025).BMI?28kg/m~2 may increase the risk of developing severe KOA(gender and age adjusted OR=1.73,95%CI= 1.29-2.33,respectively).3 ALDH1A2 genotype C/C,C/G,G/G genotype distribution in the case group frequency was 64.6%,31.7%,3.7%;Frequency distribution in the control group was 61.5%,35.9%,2.6%;the distribution between the two groups have no significant difference(chi-square = 1.03,P = 0.60),C and G gene frequency in the case group were 80.4% and 19.6% respectively,in the control group were 79.5% and 20.5% respectively,the distribution between the two groups have no significant difference(chi-square = 0.11,P = 0.75).4 IL-4 gene P1/ P1,P1 / P2,P2/ P2 frequency of genotype distribution in the case group was 59.3%,36.5%,4.2%;Frequency distribution in the control group for 38.0%,58.5%,3.5 %;the distribution of the difference between two groups was statistically significant(chi-square =18.81,P =0.00).P1 and P2 gene frequency in the case group were 77.5% and 22.5%,in the control group 67.2% and 32.8%,the distribution of the difference between two groups was statistically significant(chi-square =10.23,P =0.00).5 When stratified by cases in accordance with the knee osteoarthritis K/L hierarchical grouping examination,divided into the case group levels 3 and 4 cases,ALDH1A2 genotype C/C,C/G,G/G in the case group level 3 distribution frequency of 70.0%,25.0%,5.0%;In case group 4 distribution frequency was 62.0%,34.9%,3.1%,there was no significant difference between the distribution of the two groups(chi-square = 2.06,P = 0.36).IL-4 genotype P1/P1,P1/P2,P2/P2,in the case group level 3 distribution frequency of 66.7%,30.0%,2.0%;in case group frequency distribution was55.8%,39.5%,4.7%;the distribution of the difference between two groups was statistically significant(chi-square = 2.002,P = 0.368).6 When stratified cases according to BMI layered,the case group is divided into obese and non-obese group,ALDH1A2 genotype C/C,C/G,G/G genotype in obese group distribution frequency of 61.4%,29.5%,9.1%;Frequency distribution in non-obese group was 65.5%,32.4%,2.1%;there was no significant difference between the distribution of the two groups(chi-square = 4.67,P = 0.97).IL-4 gene P1/ P1,P1 / P2,P2/ P2 the frequency distribution of genotype in obese group was 56.8%,43.2%,0.0%;Frequency distribution in non-obese group was 60.0%,34.5%,5.5%;there was no significant difference between the distribution of the two groups(chi-square = 3.19,P = 0.20).11111111111111111111111111111111111111111111111111 11117 When stratified cases shall be carried out in accordance with the age,ALDH1A2 gene in the 60-70 age C/C,C/G,G/G genotype frequency of 68.2%,28.4%,3.4%;Frequency distribution in70-80 age was 62.2%,33.7%,4.1%;there was no significant difference between the distribution of the two groups(chi-square = 0.72,P =0.70).IL-4 gene P1/P1,P1 / P2,P2 / P2 genotype frequency of 70.5%,27.3%,2.2%;Which 70-80 age group was 48.0%,45.9%,6.1%;the distribution of the difference between two groups was statistically significant(chi-square =9.95,P =0.00).Conclusion:1 IL-4 rs3204689P1 / P2 gene loci polymorphism may be related to our country the han nationality in north China the crowd of KOA susceptibility.rs3204689 loci alleles P1 increases the risk of KOA,Further analysis showed that this effect is more pronounced with increasing age;carry P1 / P2 genotype may significantly increase the risk of KOA,this effect mainly in the 70-80 year-old individuals.2 ALDH1A2 rs8179190C/G gene loci polymorphism may not be related to our country the han nationality in north China the crowd of KOA susceptibility and severity.3 Obese patients significantly increased the risk of KOA. |
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