新生儿硬肿症并肺出血36例临床分析

目的 评价孕酮受体基因内含子G插入306碱基对多态性（PROGINS）在子宫内膜异位症发病中的意义。方法 2005-06—2006-06中国医科大学附属二院和解放军463医院将66例手术及组织学证实诊断的子宫内膜异位症患者和非子宫内膜异位症对照组56例，通过人末梢血提取白细胞DNA，PCR检测基因型分布频率及等位基因（野生型T1和突变型T2）频率．结果 两组比较突变型T2基因型分布频率分别为子宫内膜异位症组0．14，对照组0．04，OR：4．54（95％C1：1.50—13.78），P=0.004。子宫内膜异位症组有2例纯突变型T2（3．0％）：结论 PROG1NS可能与子宫内膜异位症发病有关。     

Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage

OBJECTIVE: Proinflammatory cytokines have been described as etiologic factors in idiopathic recurrent miscarriage. We investigated the relation between idiopathic recurrent miscarriage and polymorphisms in the gene encoding for the interleukin 1 receptor antagonist, an indigenous modulator of proinflammatory immune response. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred five women with a history of three or more consecutive pregnancy losses before 20 weeks of gestation and 91 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction was performed to identify the different alleles of the gene encoding for interleukin 1 receptor antagonist. RESULT(S): Allele frequencies among women with idiopathic recurrent miscarriage and controls were 0.34 and 0.11, respectively, for the polymorphic allele 2 (P=.002; odds ratio: 7.4, confidence interval: 2.9--10.8) and.05 and.05, respectively, for the polymorphic allele 3 (P=.6; odds ratio: 1.3, confidence interval: 0.8--2.3). Allele 2 was present in homozygous form in 9% of women with idiopathic recurrent miscarriage. In contrast, 1% of the control women were homozygous for this allele (P<.001; odds ratio: 13.5, confidence interval: 7.5--21.8). CONCLUSION(S): These data support a role for allele 2 of the gene encoding for interleukin 1 receptor antagonist as genetic determinant of idiopathic recurrent miscarriage.     

A polymorphism of the interleukin-1beta gene and idiopathic recurrent miscarriage

OBJECTIVE: Proinflammatory cytokines have been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism in exon 5 of the interleukin-1beta gene (IL1B) and interleukin-1beta (IL-1beta) serum levels. DESIGN: Case control study. SETTING: Academic research institution. SUBJECTS: One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 68 healthy controls with at least two live births and no history of pregnancy loss. INTERVENTIONS: Peripheral venous puncture. MAIN OUTCOME MEASURES: An IL1B exon 5 (position +3953) gene polymorphism was analyzed by PCR amplification followed by restriction fragment length polymorphism analysis. IL-1beta serum levels were analyzed by a commercially available ELISA. RESULTS: Allele frequencies in women with IRM and controls were 77.9% and 80.8%, respectively, for the E1 allele (wild type), and 22.1% and 19.2%, respectively, for the E2 allele (mutant). No association between the E2 allele and the occurrence of IRM was found (P=.57, odds ratio =.83). Genotype frequencies and IL-1beta serum levels were not significantly different between the study group and the control group. CONCLUSIONS: This is the first report on an IL1B polymorphism in IRM. Although known to alter IL-1beta expression, the investigated IL1B polymorphism is not associated with IRM and increased serum levels in a large Caucasian population.     

The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage

OBJECTIVE:To investigate the association between the C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR), serum homocysteine levels, and idiopathic recurrent miscarriage in a Middle-European white population.METHODS:In a case control study, we investigated 133 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 74 healthy controls with at least two live births and no history of pregnancy loss. A DNA extraction and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the MTHFR C677T polymorphism. Serum homocysteine levels were assessed by a fluorescence polarization immunoassay.RESULTS:The MTHFR allele frequencies in women with idiopathic recurrent miscarriage and controls were 34.6% and 21.6%, respectively, for the T allele (mutant) and 65.4% and 78.4%, respectively, for the C allele (wild type) (P =.007, odds ratio 1.9, 95% confidence interval 1.2, 3.1). The MTHFR genotype frequencies in women with idiopathic recurrent miscarriage and controls were: 17.3% (T/T), 34.6% (C/T), 48.1% (C/C) and 5.4% (T/T), 32.4% (C/T), 62.2% (C/C), respectively (P =.03, odds ratio 3.7, 95% confidence interval 1.2, 11.8 [T/T versus C/T and C/C]). Serum concentrations of homocysteine were significantly higher in carriers of a MTHFR mutant allele compared with women with no mutant allele (mean 7.4 +/- 2.4 micromol/L [T/T + C/T] versus 6.5 +/- 2.6 micromol/L [C/C], P =.05).CONCLUSION:Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage.     

The C46T polymorphism of the coagulation factor XII gene and idiopathic recurrent miscarriage

Thrombophilia has been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the coagulation factor XII (FXII) gene. Two hundred and twelve women with a history of IRM and 149 healthy controls were tested by a mutagenically separated polymerase chain reaction assay (MS PCR). Allele and genotype frequencies were not significantly different between the study and the control groups. Our data suggest that the FXII gene is not a candidate gene for this condition.     

Tryptophan hydroxylase gene polymorphism (A218C) and idiopathic recurrent miscarriage

OBJECTIVE: To investigate the frequency of a polymorphism in intron 7 of the tryptophan hydroxylase gene among women with idiopathic recurrent miscarriage and healthy controls. METHODS: In a case control study, we studied 125 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 137 healthy controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the A218C polymorphism in intron 7 of the tryptophan hydroxylase gene. RESULTS: Allele frequencies among women with idiopathic recurrent miscarriage and controls were 32.4% and 38.7%, respectively, for allele A (wild type) and 67.6% and 61.3%, respectively, for allele C (mutant). No association between the presence of allele C and idiopathic recurrent miscarriage was found (P = .3; odds ratio 1.31; 95% confidence interval 0.93, 1.87). Genotype frequencies also were not significantly different between the study group (C/C: 44.8%; A/C: 45.6%; A/A: 9.6%) and the control group (C/C: 37.2%; A/C: 48.2%; A/A: 14.6%; P = .2). Between women with primary and women with secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed (63% vs 62% for allele C and 31% vs 38% for allele A; P = .3). CONCLUSION: The A218C polymorphism in intron 7 of the tryptophan hydroxylase gene is not associated with idiopathic recurrent miscarriage.     

PROGINS receptor gene polymorphism is associated with endometriosis

OBJECTIVE: To investigate the association between the 306-base pair insertion polymorphism in intron G of the progesterone receptor (PROGINS) and endometriosis. DESIGN: Case-control study. SETTING: Tertiary care center. PATIENT(S): Ninety-five white women with surgically diagnosed and histologically confirmed endometriosis and 107 white women without endometriosis (controls). INTERVENTION(S): Determination of PROGINS was performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and distribution of the PROGINS allele. RESULT(S): Frequencies of the mutant allele T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio, 2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women with endometriosis and 0.9% of controls. CONCLUSION(S): PROGINS appears to be associated with endometriosis in white persons.     

Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis

Background

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent.

Aim of the study

To evaluate the association between the PROGINS polymorphism and the risk of endometriosis.

Methodology

A meta-analysis of 12 published case–control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism.

Results

An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41–1.43, p = 0.15–0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11–0.15). Reanalysis without the studies whose controls deviated from the Hardy–Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19–1.22, p = 0.19–0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52–2.72, p = 0.0008–0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70–0.74, p = 0.54–0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I ² = 38–70 %), except in the European subgroup, which had zero heterogeneity (I ² = 0 %) in all genetic models, as did all homozygous and recessive effects.

Conclusion

This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.     

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage

OBJECTIVE: To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. RESULT(S): No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. CONCLUSION(S): This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.     

Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population

Purpose  

Recurrent pregnancy loss (RPL) could be caused by insufficient progesterone in the luteal phase of menstruation and early pregnancy. Progesterone plays a critical role in oocyte maturation, embryo implantation and placenta maintenance in early gestation. This study was set out to investigate the association between polymorphisms of the progesterone receptor (PGR) gene and idiopathic RPL.     

Association of progesterone receptor polymorphism with recurrent abortions

OBJECTIVE: The current study sought for polymorphisms within the progesterone receptor (PR) gene. Allele and genotype frequencies of patients with repeated abortions were compared to a control group. DESIGN: All exons of the PR of 42 women with repeated abortions and 40 controls were screened for single nucleotide polymorphisms (SNP). Determination of the DNA-sequences was performed. RESULTS: Three SNPs were detected (exon 1: G1031C Ser344Thr; exon 4: G1978T Leu660Val, exon 5: C2310T His770His). These SNPs are linked. The more frequent wildtype (*1) allele and the rarer (*2) allele were found in the control group and in the study group at different frequencies (control group: *1/*1: 78%, *1/*2: 22%, *2/*2: 0%; patient group: *1/*1: 50%, *1/*2: 43%, *2/*2: 7%). The genotypes distributions differed significantly from each other (P=0.019, chi2=7.879). CONCLUSIONS: The data suggest that the rarer PR allele may be associated with an increased likelihood of repeated miscarriages contributing to its multi-factorial causes.     

The insulin-like growth factor 2 receptor gene Gly1619Arg polymorphism and idiopathic recurrent spontaneous abortion

Abstract

Objective.?The insulin-like growth factor 2 (IGF2) and its receptor (IGF2R) are important regulators of placental function and fetal growth. Our aim was to investigate the association between IGF2R gene Gly1619Arg G>A polymorphism and recurrent spontaneous abortion (RSA).

Methods.?Polymerase chain reaction and restriction fragment length polymorphism methods were performed to identify the genotypes in 149 couples with a history of at least three consecutive spontaneous abortions and 149 age-matched, unrelated, and fertile couples.

Results.?There were no statistically significant differences in genotype or allele frequency among the couples with RSA and healthy controls.

Conclusions.?We found no evidence that the IGF2R Gly1619Arg variation is associated with RSA.     

The association of arylendosulfatase 1 (SULF1) gene polymorphism with recurrent miscarriage

Purpose

One of the most common problems in reproductive medicine is recurrent miscarriage (RM). There is increasing evidence showing genetic susceptibility of women is an important risk factor in the occurrence of RM. In recent years, there is a growing interest in sulfate and its role in fetal development. A novel mechanism of SULF1 has been demonstrated for modifying the activities of some growth factors and signalling molecules that have major roles during embryogenesis. The aim of present study was to evaluate the association of SULF1 gene polymorphism (rs6990375 G > A) in Iranian patients with RM.

Methods

We established a case-control study of 200 Iranian women: 100 patients with the history of two or more RM as cases and 100 healthy women with at least two cases of successful pregnancy and no history of miscarriage as controls. The polymorphism was examined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.

Results

The genotypic analysis between case and controls showed significant differences (p-value = 0.000). Allelic analysis showed no significant correlation (Χ2 = 3.36, p-value = 0.066). The heterozygous genetic variant was significantly higher among healthy women (OR = 12.67, 95 % CI = 6.47–24.79).

Conclusions

Our data showed that rs6990375 polymorphism of SULF1 gene could be among one of the factors related to RM in Iranian women. Further evaluation of this polymorphism may be important and need further studies.     

Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.     

HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage

HLA-G is a class 1 major histocompatibility complex gene that is expressed in cytotrophoblasts at the materno-fetal interface. It has been suggested that HLA-G could play a key role in materno-fetal immunological interactions during pregnancy. To investigate whether there is an association between HLA-G locus and recurrent spontaneous miscarriage, HLA-G alleles were determined by a PCR-RFLP method in 38 couples with recurrent spontaneous miscarriage and in 26 random control couples. In this series parental HLA-G sharing, extended HLA-G/A haplotypes and the frequencies of the HLA-G alleles were similar in the two groups. Thus, our data suggest that there is no detectable relation between susceptibility to recurrent spontaneous miscarriage and HLA-G locus.     

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in S?o Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The chi(2) test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.