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Study on the Association of SNPs of nm23 Gene with the Risk of Endometriosis in North Chinese Women

Author: ZhaoZuo
Tutor: KangShan；LiZuo
School: Hebei Medical University
Course: Obstetrics and Gynaecology
Keywords: endometriosis nm23 gene promoter region single nucleotide polymorphism risk
CLC: R711.71
Type: Master's thesis
Year: 2011
Downloads: 48
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Abstract

Objective:Endometriosis is one of the most common gynaecological diseases, which is defined as the growth of endometrial glands and stroma outside the uterine cavity, such as the ovary and the peritoneal surface. It affects 8–10% of women of reproductive age. Main symptoms are pelvic pain, dysmenorrhea and infertility. Until now no single theory can fully explain the etiology and pathogenesis of the disease. Although endometriosis is generally considered a benign disorder, it does exhibit some characteristics with cancer, such as clonality, local invasion and aggressive spread to distant organs tissues. Recently, growing evidence suggests that the altered tumor suppressor genes might be related to the development of endometriosis. The nm23 gene has been proposed as a candidate tumor metastasis suppressor,which was indicated when transfection of murine nm23 into the highly metastatic melanoma subline K1735 TK resulted in significantly reduced metastasis. Schneider J and kong et al. found that nm23 may play a still undefined role in its pathogenesis. Several single-nucleotide polymorphisms (SNPs) in the nm23 have been examined. Among them, two SNPs including rs16949649 T/C and rs2302254 C/T have been studied to be associated with the risk of several diseases. On the basis of these findings, we hypothesized that the two SNPs (rs16949649 T/C and rs2302254 C/T) located in the promoter region of the nm23 gene may be associated with susceptibility to endometriosis in our Chinese sample. So we conducted a case–control study to test for the possible association between nm23 gene polymorphisms and the risk of endometriosis.Methods: This case-contral study included 379 patients with endometriosis and 384 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 nm23 rs16949649T/C and rs2302254C/T genes were analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was performed using SPSS13.0 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 nm23 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 The distribution of the nm23 rs16949649T/C and rs2302254C/T 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 nm23 rs16949649T/C(T/T, T/C and C/C) in patients and controls were 36.4%、43.3%、20.3% and 39.3%、43.5%、17.2%, respectively; the allele frequencies(T and C) in patients and controls were 58.0%、42.0% and 61.1%、38.9%, respectively. There was no statistically significant difference in the genotype distributions or allele frequencies of nm23 rs16949649T/C between the patients and controls (P>0.05). Compared with the C/T+T/T genotypes, the C/C genotype could not significantly modify the risk of developing endometriosis. The odds ratio was 0.81(95%CI= 0.57~1.17).3 The genotype frequencies of the nm23 rs2302254C/T(C/C, C/T and T/T) in patients and controls were 57.3%、37.5%、5.3% and 56.0%、36.5%、7.6%, respectively; the allele frequencies(C and T) in patients and controls were 76.0%、24.0% and 74.2%、25.8%, respectively. There was also no significant difference in genotype and allele distributions of the nm23 rs2302254C/T between the two groups (P>0.05). Compared with the C/T+C/C genotypes, the T/T genotype could not increase the risk of developing endometriosis, the odds ratio was 1.46(95%CI= 0.81~2.64).4 The promoter polymorphisms rs16949649T/C and rs2302254C/T displayed linkage disequilibrium (D’=0.82). The frequencies of four haplotypes (rs16949649T/rs2302254C, rs16949649T/rs2302254T, rs16949649C/rs23022 54C and rs16949649C/rs2302254T) of rs16949649T/C and rs2302254C/T were not significantly different between the case and control groups (P=0.557).Conclusions: 1 The nm23 gene promoter rs16949649T/C polymorphism was not associated with susceptibility to endometriosis.2 No significant association of the rs2302254C/T polymorphism with the risk of developing endometriosis.3 Although the rs16949649T/C and rs2302254C/T SNPs displayed linkag-e disequilibrium, there were no associations between four haplotypes (rs16949649T/rs2302254C, rs16949649T/rs2302254T, rs16949649C/rs2302254C and rs16949649C/rs2302254T) and the risk of endometriosis development.

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