| Objective: Endometriosis (EMs) and adenomyosis are common gynecological diseases, which are produced by multiple gene loci interacting with each other and with the environment. These two diseases can bring chronic pelvic pain and infertility for women of reproductive age. Although there are various methods to cure them, the result is unsatisfactory, and the reason due to the fact that aetiology and pathogenesis are not completely understood to date. It is the widely accepted that endometriosis is caused by the blood of menstruate countercurrented, while adenomyosis is caused by the decreased capacity of recovery for the muscular wall of the uterus. However, the endometrial cells implant either outside the uterine cavity or within the myometrial wall of the uterus, if implantation of these endometrial tissues intends to be successful, one of the requisition for the development of endometriosis must be angiogenesis. Vascular endothelial growth factor (VEGF) is a prime regulator of physiological and pathological angiogenesis in known as angiogenic factor. It can directly and designedly act on endothelial cell of blood vessel and result in neovascularization. Some single nucleotide polymorphisms (SNPs) in the promoter regions of human VEGF gene may influence protein expression by altering VEGF gene transcribe activity. Studies have shown that the VEGF -460C/T, -1154G/A polymorphisms were associated with the risk of some diseases. Our purpose was to analysis the association of VEGF -460C/T, -1154G/A SNPs with the risk of endometriosis and adenomyosis and further illuminate molecular biology mechanisms of endometriosis and adenomyosis.Methods: This case-contral study included 344 patients with endometriosis and 360 frequency-matched healthy control women; 174 patients with adenomyosis and 199 frequency- matched healthy control women. Five milliliter of venous blood from each subject was drawn in Vacutainer tubes containing EDTA and stored at 4℃, while the information of every subject was obtained. The genomic DNA was extracted within one week after bleeding by using proteinase K digestion followed by a salting out procedure. Genotypes of the VEGF -460C/T, -1154G/A genes were analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was performed using SPSS11.5 software package. A probability level of 5% was considered significant. The age difference of cases and frequency-matched controls was analyzed by the t-test. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the VEGF genotype and allelotype distribution in patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression model.Results: 1 Age, menarche age, gravidity and parity among endometriosis, adenomyosis and control women had no significant difference (P>0.05). The distribution of the VEGF -460C/T, -1154G/A genotypes in the control group did not significantly deviate from that expected for a Hardy-Weinberg equilibrium (P>0.05). 2 The genotype frequencies of the VEGF -460C/C, C/T and T/T in endometriosis and controls were 3.8%/4.7%, 37.8%/31.7% and 58.4%/63.6%, respectively; the C and T allele frequencies were 22.7%/20.6% and 77.3%/79.4%, respectively. There was no statistically significant difference in the genotype distributions or allele frequencies of VEGF -460C/T between the cases and controls (P>0.05; Table II). Compared with the C/T+T/T genotypes, the C/T genotype could not significantly modify the risk of developing endometriosis. The odds ratio was 0.80 (95% CI=0.59~1.09). 3 The genotype frequencies of the VEGF -460C/C, C/T and T/T in adenomyosis and controls were 4.0%/6.0%, 33.3%/32.2% and 62.6%/61.8%, respectively; the C and T allele frequencies were 20.7%/22.1% and 79.3%/77.9%, respectively. There was no statistically significant difference in the genotype distributions or allele frequencies of VEGF -460C/T between the cases and controls (P>0.05; Table II). Compared with the C/T+T/T genotypes, the T/T genotype could not significantly modify the risk of developing endometriosis. The odds ratio was 1.04 (95% CI=0.68~1.58). 4 The genotype frequencies of the VEGF -1154 A/A, G/A, and G/G in endometriosis and controls were 1.7%/5.8%, 28.8%/32.8% and 69.5%/61.4%, respectively; the A and G allele frequencies were 16.1%/22.2% and 83.9%/77.8%, respectively. There was significant difference in genotype and allele distributions of the VEGF -1154G/A between two groups (P=0.006, 0.004, respectively) (Table II). Compared with the G/A+ A/A genotypes, the G/G genotype significantly increased the risk of developing endometriosis. The odds ratio was 1.43 (95% CI=1.05~1.96). 5 The genotype frequencies of the VEGF -1154 A/A, G/A, and G/G in adenomyosis and controls were 2.9%/7.0%, 23.6%/34.2% and 73.6%/58.8%, respectively; the C and T allele frequencies were 20.7%/22.1% and 79.3%/77.9%, respectively. There was significant difference in genotype and allele distributions of the VEGF -1154G/A between two groups (P=0.007, 0.001, respectively) (Table II). Compared with the G/A+ A/A genotypes, the G/G genotype significantly increased the risk of developing adenomyosis. The odds ratio was 1.95 (95% CI=1.26~3.03). 6 The promoter polymorphisms -1154G/A and the -460C/T was not linkage disequilibrium (D'=0.347).Conclusions: 1 VEGF -1154G/A polymorphism was associated with susceptibility to endometriosis and adenomyosis, carrying G allele may significantly increase the risk of developing endometriosis and adenomyosis. 2 No significant association of the -460C/T polymorphism with the risk of developing endometriosis and adenomyosis. 3 The promoter polymorphisms -1154G/A and the -460C/T were not linkage disequilibrium. |
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