Plasminogen activator inhibitor-1 4G/5G polymorphism and susceptibility to endometriosis in the Italian population

Objectives

Some controversy exists for the potential association of the plasminogen activator inhibitor-1 (PAI-1) gene polymorphism 4G/5G and susceptibility to endometriosis. To clarify this issue, we have examined the prevalence of this polymorphism in a case–control study in the Italian population.

Study design

The PAI-1 4G/5G polymorphism was evaluated in n = 368 reproductive year aged Caucasian women who underwent gynaecological laparoscopy for chronic pelvic pain, infertility, ovarian cysts and myomas. A second group of controls included n = 329 normal subjects.

Results

The 697 women enrolled were divided as follows: the endometriosis group (n = 204), the gynaecological control group (n = 164) and the general population control group (n = 329). No statistical significant differences emerged between endometriosis patients and gynaecological controls with regard to the allele frequencies and co-dominant and dominant models of genotype distribution. A borderline statistical difference was only observed for the recessive model of inheritance in which, contrary to previous findings, the PAI-1 4G/4G genotype seems to be less linked to the disease development.

Conclusion

The findings reported herein do not support the previously reported data indicating a greater susceptibility to endometriosis in patients harbouring the PAI-1 4G/5G and 4G/4G genotypes and exclude a significant role of polymorphism in endometriosis development.     

Association of GSTP1 −313A/G polymorphisms and endometriosis risk: a meta-analysis of case–control studies

Objectives

In view of the controversies surrounding the association of glutathione S-transferases (GST) P1 with endometriosis, a meta-analysis of GSTP1 −313A/G polymorphism with endometriosis risk was performed.

Study design

The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct and Chinese Biomedical Literature Database (CBM) until March 2013. The association between GSTP1 −313A/G polymorphism and endometriosis risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95% CIs).

Results

A total of eight case–control studies were eventually identified. We found that GSTP1-313A/G polymorphism was not associated with endometriosis risk in the overall population (A vs. G: OR = 1.02, 95% CI = 0.97–1.07, P = 0.511; AA vs. GG: OR = 1.02, 95% CI = 0.98–1.06, P = 0.359; GA vs. GG: OR = 1.03, 95% CI = 0.98–1.08, P = 0.299; AA vs. GA/GG: OR = 1.01, 95% CI = 0.96–1.07, P = 0.621; AA/GA vs. GG: OR = 1.00, 95% CI = 0.97–1.03, P = 0.972). In the sub-group analysis based on ethnicity, a significant association was found in Caucasians under the recessive model (AA vs. GA/GG: OR = 1.28, 95% CI = 1.08–1.53, P = 0.006).

Conclusions

GSTP1 −313A/G polymorphism may not be associated with endometriosis risk, while the observed increase in risk of endometriosis may be due to small-study bias. Considering the limited sample size and ethnicity included in our meta-analysis, an updated meta-analysis will be urgently needed when further larger and well-designed studies are published.     

Association between endometriosis and polymorphisms in insulin-like growth factor binding protein genes in Korean women

Objective

Genetic factors are known to be associated with the development and progression of endometriosis, but the genes related to endometriosis have not been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed to be involved in the proliferation and apoptosis of cells that play an important role in the pathophysiologic mechanism of endometriosis. This study aimed to determine the association between endometriosis and polymorphisms of the IGFBP genes in Korean women.

Study design

In a case–control study, the rs1995051, rs1065780 and c.759A > G single nucleotide polymorphisms (SNPs) in the IGFBP1 gene and the −672A > G, −202A > C and c.95C > G SNPs in the IGFBP3 gene were analyzed in 128 women with endometriosis and 108 normal control women.

Results

The haplotype genotype composed of a combination of three IGFBP1 gene polymorphisms was not related to endometriosis, while the haplotype genotype of the IGFBP3 gene had a significant association with endometriosis. Women not carrying the AAG (−672A/−202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have a 3.19-times higher risk of endometriosis compared with women with AAG homozygotes, and this trend was found in women with advanced endometriosis but not in women with early endometriosis.

Conclusions

The AAG haplotype allele of the −672A > G, −202A > C and c.95C > G polymorphisms in the IGFBP3 gene may be associated with advanced endometriosis in Korean women.     

A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women

Objective

MicroRNAs (miRNAs) play critical roles in cervical carcinogenesis. Common single nucleotide polymorphisms (SNPs) in pre/pri-miRNAs may change their property through altering miRNAs expression and/or maturation. Here we aimed to investigate the influence of three common SNPs in pre/pri-miRNAs (pri-miR-26a-1 rs7372209, pre-miR-27a rs895819 and pri-miR-100 rs1834306) on individual susceptibility to cervical cancer.

Methods

We genotyped these three polymorphisms in 103 cervical cancer cases and 417 cancer-free female subjects using polymerase chain reaction–ligation detection reaction (PCR–LDR) method. Unconditional logistic regression analysis was utilized to estimate the association between these polymorphisms and the risk of cervical cancer.

Results

In a logistic regression analysis, we found that the rs895819 polymorphism in pre-miR-27a exhibited a significant effect on cervical cancer risk; T allele (OR = 0.68, 95% CI = 0.49–0.95, P = 0.025), and CT (OR = 0.33, 95% CI = 0.15–0.74, P = 0.007) or TT (OR = 0.33, 95% CI = 0.15–0.72, P = 0.006) genotype were associated with the decreased risk, compared to C and CC respectively. As we used further genotype association models, we found a similar trend of the association in additive (OR = 0.70, P = 0.041) and recessive model (OR = 0.33, P = 0.004). We did not detect any association of the other two SNPs in pri-miR-26a-1 (rs7372209) and pri-miR-100 (rs1834306) with cervical cancer risk.

Conclusion

Our study provides the first evidence that the miR-27a rs895819 polymorphism is associated with a decreased risk of cervical cancer in southern Chinese women.     

Polymorphic variants of DNMT3A and the risk of endometriosis

Objective

Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis. We aimed to study whether DNMT3A polymorphisms could be a genetic risk factor for endometriosis and endometriosis-related infertility.

Study design

We studied 5 SNPs (rs2289195, rs7590760, rs13401241, rs749131 and rs1550117) located in the DNMT3A gene in 357 women with endometriosis and 640 controls.

Results

We did not observe significant differences between genotype and allele frequencies of rs2289195, rs7590760, rs13401241, rs749131 and rs1550117 SNPs in women with endometriosis, endometriosis-related infertility, and controls. The lowest p values of the trend test were observed for DNMT3A rs1550117 in endometriosis and endometriosis-related infertility (p_trend = 0.049 and p_trend = 0.055, respectively).

Conclusions

Our results did not supply evidence for the contribution of SNPs located in DNMT3A to either endometriosis or endometriosis-related infertility.     

Determination of cathepsins B,D and G concentration in eutopic proliferative endometrium of women with endometriosis by the surface plasmon resonance imaging (SPRI) technique

Objective

To determine the concentrations of cathepsins B, D and G in proliferative eutopic endometrium of patients with and without endometriosis, by use of the surface plasmon resonance imaging (SPRI) technique.

Study design

A total of 55 patients were recruited in the study: 31 patients with endometriosis (stages I–IV) and 24 controls. Endometrial samples were obtained in the first phase of the menstrual cycle from regularly menstruating premenopausal women, prior to laparoscopy, by the use of aspiration biopsy. Endometriosis was appropriately classified according to the Revised American Fertility Society classification and confirmed by histopathology in every case. The SPRI technique was used to determine the concentration of cathepsins B, D and G. To compare the two groups for quantitative data, Mann–Whitney–Wilcoxon's test was used due to the non-normal distribution of the tested variables and normality of distribution was assessed using Shapiro–Wilk W test.

Results

The concentration of the three examined cathepsins was higher in the proliferative eutopic endometrium of patients with endometriosis, especially in advanced stages, e.g. III and IV, when compared to healthy individuals. Corresponding median values were, for cathepsin B: [7.93 pmol/mg (min–max 2.82–15.71) vs 1.2 pmol/mg (min–max 0.7–15.49) p = 0.0014], for cathepsin D: [1.86 pmol/mg (min–max 0.51–5.4) vs 1.03 pmol/mg (min–max 0.4–2.72) p = 0.00041] and for cathepsin G: [0.6 pmol/mg (min–max 0.33–2.51) vs 0.3 pmol/mg (min–max 0.16–1.29) p = 0.00051].

Conclusions

Increased concentrations of cathepsins B, D and G in the proliferative eutopic endometrium may play a role in the implantation of endometrial tissue outside the uterine cavity.     

The occurrence of endometriosis with ovarian carcinomas is not purely coincidental

Objective

To explore the association between epithelial ovarian cancer (EOC) and common benign gynecological disorders.

Study design

The medical records of 226 patients with EOC treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histological evaluations had been performed to determine the presence of coexisting pelvic endometriosis (n = 17), uterine leiomyoma (n = 66), adenomyosis (n = 22), or endometrial polyps (n = 17).

Results

Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was more likely associated with clear cell or endometrioid ovarian carcinoma, but less likely with high grade serous cancer. No differences were observed in the concurrence of uterine myoma, adenomyosis or endometrial polyps among the different subtypes of EOC.

Conclusions

In contrast to other common benign gynecological disorders, endometriosis showed close relationships with the clear cell and endometrioid subtypes of EOC specifically.     

The impact of IVF procedures on endometriosis recurrence

Objective

In infertile women with endometriosis requiring an in vitro fertilization (IVF) procedure, the potential risk of an IVF-related progression of the disease remains a matter of debate. Thus, since available data on this issue are scanty and controversial, an observational study has been herein conducted in order to clarify this issue.

Study design

We recruited 233 women with endometriosis who underwent IVF cycles in our unit. Patients were contacted to assess whether they experienced recurrences of the disease after IVF. The main outcome was to evaluate the impact of the number of IVF cycles and the responsiveness to ovarian hyperstimulation on the likelihood of recurrence. Clinical characteristics of women who did and did not have a recurrence were compared.

Results

One hundred and eighty-nine women were included, 41 of whom (22%) had a diagnosis of endometriosis recurrence. The 36 months cumulative recurrence rate was 20%. The number of IVF cycles and the responsiveness to ovarian hyperstimulation were not associated with the risk of disease recurrence. The adjusted OR for recurrences according to the number of started cycles was 0.92 (95% CI: 0.77–1.10) per cycle (p = 0.35). The adjusted OR for recurrences in women with intact versus compromised ovarian reserve was 0.80 (95% CI: 0.40–1.58) (p = 0.52).

Conclusions

IVF procedures do not seem to influence the likelihood of endometriosis recurrence.     

Luteinizing hormone β-subunit gene (LHβ) polymorphism in infertility and endometriosis-associated infertility

Objective

To establish the frequency of LHβ G1502A polymorphism in infertile women with endometriosis, infertile women without endometriosis and a control group.

Study design

Case-control study including 110 infertile women with endometriosis, 84 infertile women without endometriosis and a control group consisting 209 healthy fertile women recruited from the ABC School of Medicine. The LHβ G1502A polymorphism was studied by RPLP-PCR (restriction fragment length polymorphism-polymerase chain reaction).

Results

Genotypes GG, GA and AA of the LHβ G1502A polymorphism presented frequencies of 54.6%, 31.8% and 13.6%, respectively, in the women with endometriosis (p = 0.0398); of 52.4%, 38.1% and 9.5% (p = 0.0123), respectively, in the infertile women without endometriosis; and of 68.9%, 21.5% and 9.6%, respectively, in the control group. In patients with minimal/mild endometriosis and moderate/severe endometriosis, the GG, GA and AA genotype frequencies were, respectively, 47.3%, 36.4% and 16.3% (p = 0.0118); and 61.8%, 27.3% and 10.9% (p = 0.5975). Considering the alleles, allele G was present in 70.5% of the patients with endometriosis, 71.4%% of the infertile women without endometriosis and in 79.7% of the controls, whereas allele A was present in 29.5%, 28.6% and 20.3%, respectively, in the infertile women with endometriosis (p = 0.0121), infertile women without endometriosis (p = 0.0409) and controls. Alleles G and A presented frequencies of 65.5% and 34.5% and 75.5% and 24.5%, respectively, in minimal/mild endometriosis (p = 0.0026) and moderate/severe endometriosis (p = 0.4062).

Conclusion

The data suggest that LHβ G1502A polymorphism may be involved in the predisposition to infertility and minimal/mild endometriosis-associated infertility, although endometriosis might be only a coincidental finding along with infertility.     

Characteristics of clear cell ovarian cancer arising from endometriosis: A two center cohort study

Objective

Endometrioid and clear cell ovarian tumors have been referred to as “endometriosis associated ovarian cancers”. However, very few studies have compared clinical and prognostic features of endometriosis-associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database.

Methods

Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n = 27 and n = 46, respectively). Clinical and pathological data have been compared.

Results

Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4 ± 10.0 and 58.4 ± 11.2 years, p = 0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p = 0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates.

Conclusions

Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading.     

Peritoneal fluid concentrations of β-chemokines in endometriosis

Objective

To examine whether the levels of MCP-1, RANTES and MCP-3 in the peritoneal fluid correlate with endometriosis.

Study design

Patients with endometriosis were compared with controls. Setting: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. Subjects: This study involved 95 women of reproductive age who were undergoing laparoscopy for evaluation of infertility or for pelvic pain. They were divided into an endometriosis group (n = 54) and a control group (n = 41). Interventions: Peritoneal fluid samples were obtained and β-chemokines (MCP-1, RANTES and MCP-3) were measured using ELISA. Statistical analysis: Mean and median values were used to present values. Due to the non-normality of chemokines, a log transformation was applied. Differences were examined using independent samples t-test. One-way ANOVA and Tukey HSD multiple comparison post hoc tests were applied. A significance level at 0.05 was set.

Results

The levels of MCP-1 are higher (p for log values = 0.024) in the control group (mean = 687.6, SD = 467.7 pg/ml) than those of the endometriosis group (mean = 570.4, SD = 633.1 pg/ml). The same is true for the median values of MCP-1 (control median = 568.5, endometriosis median = 384.7 pg/ml). MCP-3 and RANTES do not differ significantly (MCP-3 p = 0.787, RANTES p = 0.153). The levels of MCP-1 in patients with stage II endometriosis are significantly lower in comparison with stage III (p = 0.048) and stage IV (p = 0.033) endometriosis.

Conclusions

A decrease in the concentrations of MCP-1 in stage I endometriosis has been observed, which is even larger in stage II, in contrast to stage III and stage IV endometriosis, which exhibit concentrations similar to the controls.     

Polymorphisms of FAS and FAS ligand genes in preeclamptic women

Objectives

This study investigated the influence that Fas and Fas ligand gene polymorphisms might have on preeclampsia. The pathogenesis of preeclampsia is still enigmatic and several studies have proposed that it may, in part, be determined by genetic susceptibility. Therefore, the identification of a gene polymorphism associated with an increased risk of preeclampsia might well represent a useful tool in the identification of at risk pregnant women enabling the setup of preventive therapy.Apoptosis has also been implied in the pathogenesis of preeclampsia and since Fas and Fas ligand are the main apoptotic pathway members, they may represent candidate genes involved in the development of preeclampsia.A polymorphism at the 670 position (A–G) in the Fas gene has been found more frequently in Hungarian women with preeclampsia.

Study design

The study cohort was a group of 50 women with preeclampsia and 142 healthy control subjects from the general Italian population. They were studied, by RFLP analysis, to validate the role that the 670 G Fas gene polymorphism plays in preeclampsia, and to evaluate the Fas ligand IVS2nt 124 G polymorphism. The Fisher's exact test was used to compute the statistical difference between groups.

Results

The presence of the 670 G Fas gene variant was observed in 42 preeclamptic patients (84%) and 96 members of the general population control group (67.6%) (p = 0.029). Regarding the Fas ligand gene, the IVS2nt 124 G variant was present in 14 preeclamptic patients (28%) and in 47 of the general population control subjects (33.1%) (p = 0.6).

Conclusions

The present study validated the hypothesis that the Fas 670 G variant may have an influencing role in preeclampsia.     

Comparison of clinical outcomes of patients with clear cell and endometrioid ovarian cancer associated with endometriosis to papillary serous carcinoma of the ovary

Objective

The aim of this investigation was to compare outcomes of patients with clear cell carcinoma (CCC) and endometrioid carcinoma (EC) of the ovary associated with endometriosis to patients with ovarian papillary serous carcinoma (PSC).

Methods

Patients with CCC and EC of the ovary associated with endometriosis were identified and matched by age and stage to PSC controls. Student's t test and chi square test were used to analyze continuous and categorical data. The Kaplan–Meier method was used for survival analysis.

Results

67 cases associated with endometriosis were identified, of which 45 were arising in endometriosis. Cases were matched to 134 PSC controls. 27 patients with tumors associated with endometriosis presented at stage I (40.3%), 27 at stage II (40.3%), ten at stage III (14.9%) and three at stage IV (4.5%). There was no difference in rate of optimal cytoreduction or response to chemotherapy in cases vs. PSC controls. There was a significant increase in synchronous endometrial cancer in tumors associated with endometriosis compared to PSC (25.4% vs. 3.7%; P < 0.001). 18 cases (26.9%) had recurrent disease vs. 55 (41%) controls (P = 0.03). The 5-year disease-free survival (DFS) and overall survival (OS) of patients with tumors associated with endometriosis compared to PSC controls were 75% vs. 55% (P = 0.03) and 85% vs. 77% (P = 0.2), respectively.

Conclusions

Patients with tumors associated with endometriosis had a higher rate of synchronous endometrial cancer. Cases also demonstrated a lower rate of recurrence and improved 5 year DFS; however, this did not translate into a difference in OS.     

Biopsychosocial correlates of persistent postsurgical pain in women with endometriosis

Objective

To examine pain and biopsychosocial correlates over time for women with persistent postsurgical pain after surgery for endometriosis.

Methods

Cross-sectional study of women who underwent any endometriosis surgery between 2003 and 2006. Following surgery, patients completed validated questionnaires (Short-Form McGill Pain Questionnaire, 12-item Short-Form Health Survey, Beck Depression Inventory, Coping Strategies Questionnaire catastrophizing subscale). The primary outcome was pelvic pain intensity, measured by the McGill total pain score. Bivariate comparisons between each potential predictor and pain intensity were performed using the χ² and t tests, 1-way analysis of variance, and simple linear regression.

Results

In total, 79 completed the questionnaires and were included in the present analysis. The McGill affective pain score was negatively correlated with age (β-coefficient –0.12, P = 0.002) and positively correlated with catastrophization (β-coefficient 0.66, P = 0.01). Women with a history of dyspareunia scored significantly higher on the McGill total pain score (P < 0.001); there was no association between pain intensity and endometriosis severity.

Conclusion

Younger age and catastrophization are correlated with persistent pain following surgery for endometriosis. The severity of endometriosis does not predict persistent pain. Further evaluation of psychosocial factors may identify patients who are least likely to benefit from surgeries for endometriosis-associated pelvic pain.     

Genetic polymorphisms in DNA repair gene APE1, XRCC1 and XPD and the risk of pre-eclampsia

Objective

Oxidative stress has been postulated as a major contributor to placental hypoperfusion and ischemia in pre-eclampsia (PE). Reactive oxygen species (ROS) generated during placental ischemia can cause oxidative damage to nucleic acids. Base excision repair (BER) and nucleotide excision repair (NER) are major pathways responsible for removing the oxidative DNA damage. Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage.

Study design

In order to investigate the possible association between DNA repair genes and PE susceptibility, we analyzed genotype and allele distributions of APE1-148, XRCC1-194, XRCC1-399 and XPD-751 genes in 101 patients with PE and 107 healthy women. Differences in genotype distributions and allele frequencies in the cases and the controls were compared for statistical significance using the χ²-test. Haplotype frequencies were estimated using a contingency χ²-test. One-way ANOVA and Mann–Whitney U-test were used for the statistics of the clinical and biochemical parameters.

Results

No significant association between PE and the variant alleles of APE1 codon 148 (OR: 0.77, 95% CI = 0.51–1.15), XRCC1 codon 194 (OR: 0.64, 95% CI = 0.30–1.37), XRCC1 codon 399 (OR: 1.16, 95% CI = 0.78–1.74) and XPD codon 751 (OR: 1.21, 95% CI = 0.81–1.80) was observed. Results of our haplotype analysis demonstrated that there is a high linkage disequilibrium (D′: 1.0, r² = 0.042) between the haplotypes of XRCC1 codon 194 and codon 399 markers.

Conclusions

These preliminary results suggest that the polymorphic variants of APE1-148, XRCC1-194, XRCC1-399, and XPD-751 genes are not significant risk factors for PE development.     

Tratamiento de la endometriosis con 5 mg o 25 mg diarios de mifepristona durante 6 meses. Ensayo clínico aleatorizado,doble ciego

Objectives

To evaluate the safety and efficacy of 5 mg and 25 mg doses of mifepristone for the treatment of endometriosis.

Design

Randomized double-blind study.

Setting

Eusebio Hernández Hospital, Havana, Cuba.

Subjects

Twenty-six women laparoscopically diagnosed with endometriosis were included.

Treatment

Group I received one tablet of 25 mg mifepristone daily and group II received one tablet of 5 mg mifepristone daily for 6 months. Laparoscopy and endometrial biopsy were performed before and after treatment.

Variable to evaluate efficacy

Reduction in the intensity of dysmenorrhea measured by a visual analogue scale.

Results

In both groups reductions in the intensity of dysmenorrhea and dyspareunia were highly significant compared with initial values (P <.001). All the women were amenorrheic after 45 days of treatment.

Conclusions

At doses of 5 mg or 25 mg, mifepristone could be an alternative for the treatment of endometriosis.     

Bilirubin influences the clinical presentation of pre-eclampsia

Objectives

Pre-eclampsia is a placental, inflammatory disease modified by maternal anti-oxidant status to give a syndrome. In its most severe forms pre-eclampsia is followed by maternal and neonatal mortality and morbidity. Bilirubin is a known antioxidant and as such is associated with a reduced risk of cardiovascular and respiratory disease. Hence we aimed to find an association between maternal bilirubin levels and the clinical severity of the disease.

Study design

A retrospective observational study of 50,712 pregnancies, 925 of which had pre-eclampsia (1999–2010), to examine the association between bilirubin level and perinatal outcome.

Results

In women with pre-eclampsia, those with bilirubin levels in the lowest quintile were more likely to require caesarean section (p = 0.001, aOR 2.59 (1.52–5.72)). The lowest quintile of bilirubin levels is associated with an increased risk of poor maternal (p = 0.002, aOR 3.52 (95%CI 1.6–7.7)) and infant/fetal (p = 0.001, OR = 3.05 (95%CI = 1.63–5.72)) outcome.

Conclusions

Low levels of bilirubin were associated with poor maternal and infant outcomes in women diagnosed with pre-eclampsia. Bilirubin may act as an anti-oxidant in this condition and thus modify the disease.     

Association of extracellular superoxide dismutase (SOD3) Ala40Thr gene polymorphism with pre-eclampsia complicated by severe fetal growth restriction

Objective

Placental and systemic oxidative stress with an imbalance in the oxidant/antioxidant activity seems to play a central role in the pathogenesis of pre-eclampsia. The aim of our study was to examine whether two missense polymorphisms of the extracellular superoxide dismutase (SOD3) gene (Arg213Gly and Ala40Thr) are associated with pre-eclampsia in a Caucasian population from Hungary.

Study design

One hundred and fifty-nine pre-eclamptic patients and 114 normotensive, healthy pregnant women were involved in this case-control study. The SOD3 Arg213Gly and Ala40Thr genotypes were determined using the polymerase chain reaction-restriction length polymorphism (PCR-RFLP) and allele-specific amplification methods.

Results

The Arg213Gly variant was not detected in our population. There were no significant differences in the genotype and allele frequencies of the SOD3 Ala40Thr polymorphism between pre-eclamptic patients and control subjects. However, the mutant allele carriers of this polymorphism showed an increased risk for severe fetal growth restriction-complicated pre-eclampsia, which was independent of maternal age, prepregnancy BMI, primiparity and smoking status (OR: 6.07, 95% CI: 1.33–27.8, p = 0.020; adjusted OR: 4.89, 95% CI: 1.03–23.2, p = 0.046).

Conclusion

Our results suggest a role of SOD3 Ala40Thr single nucleotide polymorphism in the risk of severe fetal growth restriction-complicated pre-eclampsia. However, further studies are needed with a larger sample size to confirm our findings and to explore the exact molecular basis of this observation.     

The effect of extracellular adenosine triphosphate on the spontaneous contractility of human myometrial strips

Objectives

Extracellular ATP is involved in cell–cell signalling in a variety of tissues but its effects in tissue level signalling in the myometrium have been poorly studied to date. We hypothesised that extracellular ATP was involved in the control of myometrial contractile frequency and/or force.

Study design

In vitro study of the effect of altering the concentration of extracellular ATP on the spontaneous contractility of human myometrial strips obtained from term elective caesarean sections.

Results

Decreasing extracellular ATP levels by the ectoATP-ase agent apyrase VI (1–50 units/mL) produced a dose dependent decrease in contractile frequency (decrease of 46.3% compared with the baseline frequency at 20 units/mL, p = 0.001, n = 6). Contractility was unchanged by apyrase VII (20 units/mL), an agent with relatively greater ADPase activity, indicating an effect via ATP and not ADP. Contractile frequency increased after addition of ATP 10–100 μM (an increase to 145.8% of baseline frequency at 100 μM: 126.1–165.5%, p = 0.005, n = 7) or the ATPase inhibitor ARL at 100 μM (an increase to 136.3% of the baseline frequency: 107.1–165.5, p = 0.03, n = 7). Contractile force remained unchanged by these agents.

Conclusions

Extracellular ATP shows a dose–response relationship to contractile frequency but does not affect contractile force. Consequently it may be involved in the pacemaking mechanism for the generation of uterine contractions.