| Objective: Genes in IGF pathway involved in the occurrence and development of endometriosis plays an important role, IGFBP3 is one of IGF pathway important members. IGFBP3 gene promoter region polymorphisms affect IGFBP3 and IGF1 expression, and then influence development of diseases. This study detected three loci polymorphisms of IGFBP3 by PCR and DNA sequencing and explored their relationships with susceptibility of endometriosis, which would provide a clue for understanding the pathogenesis of endometriosis and a way of clinical diagnosis and treatment.Methods:1 Using case-control study, saturated phenol/chloroform extraction was used to extract DNA of 196 cases of ovarian endometriosis and 178 cases of normal endometrium tissue, which collected from inpatient department and policlinic of obstetrics and gynecology depaerment in Tangshan worker’s hospital group between march 2013 and march 2014, PCR amplification and gene sequencing method was used to detect IGFBP3 promoter rs2854744 A>C, rs2132570 T>G and rs2132572 A>G polymorphism.2 Genotype and allele frequency distribution of three loci polymorphisms of IGFBP3 were analysed between patient groups of different stages.The Correlation of haplotype and endometriosis through linkage analysis.3 SPSS13.0 statistical software was used to statistical analysis. Constituent ratio was used to count date. Hardy Weinberg equilibrium, comparison of genotype and allele and linkage analysis haplotype genotype and allele frequency between the different groups, comparison of genotype and allele frequency between different stage of patients were analysised by chi-square test. which P< 0.05 were considered significant differences. Odds ratio(OR) and 95% confidence interval(CI) analysising by Unconditioned logistic regression showed relative risk.Results:1 The results of Hardy Weinberg equilibrium testing showed that there were no difference between the control groups and patient groups about the genotypes frequency distribution of IGFBP3 promoter SNPs rs2854744 A>C, rs2132570 T>G and rs2132572 A>G(P>0.05),indicated in choosing the candidate gene has reached the heredity balance.2 There was no significant difference between the case groups and the control groups for AA, AC and CC genotype frequency distribution of IGFBP3 promoter rs2854744 A>C(55.1%, 35.2%, 9.7% and 62.4%, 33.7%, 3.9%, X2=5.354, P>0.05). There was significant difference between the two groups for A and C allele frequency distribution(72.7%, 27.3% and 79.2%, 20.8%, X2=4.310, P<0.05). Women carrying the C allele had a 1.43-times higher risk of endometriosis compared with women with A allele(95%CI: 1.02-2.01). There was no significant difference between early lesion groups and advanced lesion groups for AA, AC and CC genotype frequency distribution(63.3%, 28.9%, 7.8% and 48.1%, 40.6%, 11.3%, X2=4.562, P>0.05). There was significant difference between the two stages for A and C allele frequency distribution(77.8%, 22.2% and 68.4%, 31.6%, X2=4.317, P<0.05).3 There was no significant difference between the case groups and the control groups for TT, TG and GG genotype(53.1%, 36.7%, 10.2% and 57.3%, 37.1%, 5.6%) and T and G allele(71.4%, 28.6% and 75.8%, 24.2%) frequency distribution of IGFBP3 promoter rs2132570 T>G(P>0.05). There was no significant difference between early lesion groups and advanced lesion groups for TT, TG and GG genotype(48.9%, 41.1%, 10.0% and 56.6%, 33.0%, 10.4%) and T and G allele(69.4%, 30.6% and 73.1%, 26.9%) frequency distribution(P>0.05).4 There was no significant difference between the case groups and the control groups for AA, AG and GG genotype frequency distribution of IGFBP3 promoter rs2132572A>G(53.6%, 33.7%, 12.8% and 62.4%, 30.9%, 6.7%, X2=4.879, P>0.05). There was significant difference between the two groups for A and G allele frequency distribution(70.4%, 29.6% and 76.4%, 23.6%, X2=5.302, P<0.05). Women carrying the G allele had a 1.47-times higher risk of endometriosis compared with women with A allele(95%CI: 1.06-2.05). There was significant difference between early lesion groups and advanced lesion groups for AA, AG and GG genotype(62.2%, 30.0%, 7.8% and 46.2%, 36.8%, 17.0%) and A and G allele(77.2%, 22.8% and 64.6%, 35.4%) frequency distribution(P<0.05).5 The result of chains analysis of IGFBP3 promoter SNPs rs2854744 A>C and rs2132572 A>G showed four different haplotype alleles.These haplotype alleles combination in the case groups and control groups did not appear CCAA and AAGG genotypes. Genotypes in cases groups: AAAA(48.5%), ACAG(24.5%), CCGG(7.1%) and AAAG(6.6%), etc.. The genotypes in the control group: AAAA(52.3%), ACAG(19.7%), AAAG(10.1%) and ACAA(10.1%), etc. There was no significant difference between the two groups(X2=10.746, P>0.05). There was significant difference between the case and control groups for AA, AG, CA, CG haplotype allele frequency distribution(66.6%, 6.1%, 3.8%, 23.5% and 72.2%, 7.0%, 5.6%, 15.2%, X2=8.944, P<0.05). Women with the CG haplotype allele had a 1.68-times higher risk of endometriosis compared with women with AA haplotype allele(95%CI: 1.15-2.45).Conclusions:1 SNPs rs2854744 A>C and rs2132572 A>G in IGFBP3 promoter might be associated with the occurrence and development of endometriosis. People carried variant alleles may increase the risk of endometriosis.2 rs2132570 T>G in IGFBP3 promoter was not associated with the occurrence and development of endometriosis.3 SNPs rs2854744 A>C and rs2132572 A>G linkage disequilibrium in IGFBP3 promoter might be associated with the occurrence of endometriosis. People with CG haplotype alleles might increase the risk of endometriosis. |
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