Glutathione S-transferases P1-1 and A1-1 in ovarian cyst fluids

PURPOSE: The purpose of the present study was to determine the gluthathione S-transferases (GST) P1-1 and A1-1 levels in cyst fluid from malignant, borderline, and benign ovarian tumors. The clinical relevance of these enzymes in cyst fluid was investigated, including the possible relation with resistance to chemotherapy. METHODS: A total of 90 ovarian cysts were punctured for cyst fluid collection. GSTP1-1 and GSTA1-1 concentrations were determined by ELISA in cyst fluid from 23 malignant, 9 borderline, and 51 benign primary ovarian tumors, and levels were correlated with histopathological data. RESULTS: Significantly higher GSTP1-I concentrations were found in cyst fluid from malignant (median: 477 ng/ml), compared with benign (median: 52 ng/ml) ovarian cysts (p < 0.0001), as well as in fluid from borderline (median: 366 ng/ml) compared with benign cysts (p < 0.0001). No significant differences were found in cyst fluid GSTA1-1 concentrations between the histologic subgroups. In cyst fluid from malignant tumors higher GSTPI-1 and lower GSTAI-1 concentrations were found in patients with worse prognostic factors: FIGO II-III-IV, grade 2-3, residual tumor > 2 cm, presence of ascites, patients with recurrent disease, and survival, but differences were not significant. In the subgroup of patients that received cisplatin-based chemotherapy (n = 14) significantly higher GSTP1-1 (p = 0.01) concentrations were found in patients with recurrence compared with patients without recurrence. Considering only FIGO stage I patients, a differentiation could be made between patients with or without recurrence based on cyst fluid GSTP I - I concentrations. CONCLUSIONS: Determination of glutathione S-transferases P 1-1 in cyst fluid samples from ovarian tumors can be of additiona] value in the differentiation between histologic subgroups. In case of possible low malignant potential cysts where sampling of the most representative tissue can be an issue, determination of GSTP- I concentrations in cyst fluid may optimise histopathologic classification. Cyst fluid GSTP1-1 seems to be a good marker for aggressiveness of the ovarian tumor, and it may predict response to chemotherapy.     

CYP1A1 MspI多态性及其合并GSTM1基因缺失与子宫内膜异位症的关系

目的:探讨新疆维吾尔族、汉族人群中解毒酶细胞色素P4501A1(CYP1A1)基因MspI多态性、CYP1A1/MspI合并GSTM1基因缺失基因型与子宫内膜异位症(内异症)的关系。方法:用聚合酶链反应限制性片段长度多态性技术,检测维吾尔族107例正常妇女与41例内异症患者、汉族105例正常妇女与80例内异症患者CYP1A1基因限制性内切酶MspI位点的3种基因型的分布频率。结果:CYP1A1基因MspI位点基因型在维吾尔族正常对照组的分布频率为TT(48.6%)、TC(42.9%)、CC(8.5%),等位基因分布频率为T(70.1%)、C(29.9%),内异症组的基因型分布频率为TT(39.1%)、TC(46.3%)、CC(14.6%),等位基因分布频率为T(62.2%)、C(37.8%),差异无显著性(P>0.05);在汉族正常对照组基因型分布频率为TT(41.9%)、TC(46.7%)、CC(11.4%),等位基因分布频率为T(65.2%)、C(34.8%),内异症组基因型分布频率为TT(42.5%)、TC(51.2%)、CC(6.3%),等位基因分布频率为T(68.1%)、C(31.9%),差异无显著性。两个民族对照组之间与内异症组之间基因型频率与等位基因频率比较差异无显著性。在CYP1A1/MspI合并GSTM1(/)基因型的人群中,维吾尔族对照组与内异症组的基因型频率与等位基因频率分布比较均有显著差异(P<0.05),其TC+CC与TT比较,OR值为3.556(P<0.05)。汉族对照组与内异症组的比较无统计学差异。结论:解毒酶CYP1A1基因MspI多态性本身可能与维吾尔族及汉族内异症发病无关,而CYP1A1/MspI合并GSTM1(/)基因型可能与维吾尔族内异症发病有关。     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.     

Analysis of GSTM1, GSTT1, and CYP1A1 in idiopathic male infertility

Enzymes belonging to the glutathione-S-transferase (GST) and cytochrome P450 (CYP) families are involved in a 2-stage detoxification process of a wide range of environmental toxins and carcinogens. In order to investigate whether there is a genetic association of the biotransformation enzymes and idiopathic male fertility, we studied GSTT1, GSTM1, and CYP1A1*2A polymorphisms in 150 infertile men and 200 healthy men as controls from Northern Iran. Genotyping of the GSTT1 and GSTM1 genes were performed using the multiplex polymerase chain reaction (PCR). However, the CYP1A1 polymorphism was determined using PCR-restriction fragment length polymorphism (RFLP). The GSTM1 and GSTT1 null genotypes were present at frequencies of 0.61 and 0.34 in infertile cases, whereas in controls the frequencies were 0.33 and 0.17, respectively. Double-null genotype was found to be elevated among infertile men (odds ratio [OR] = 3.75, 95% confidence interval [CI] = 2.42-6.45; P < .0001). The frequency of TT, TC, and CC genotypes of CYP1A1 polymorphism in the controls were 42.5%, 45.5%, and 12%, respectively, while those in the infertile men were 38.7%, 48%, and 13.3%. The CYP1A1*2A did not display any association with male infertility. We observed an association between male infertility and the GSTM1 and GSTT1 null deletion, but not with the CYP1A1 polymorphism in North Iranian men with idiopathic infertility.     

Evaluation of UGT1A1 and SULT1A1 polymorphisms with lipid levels in women with different hormonal status

Background.?Estrogens influence many physiological processes including cardiovascular health. Polymorphisms in phase I and II estrogen metabolism enzymes are associated with lipid levels in women.

Methods.?A cross-sectional study was carried out with 269 postmenopausal women, 116 who received oral hormonal therapy (HT) (39–75 years) with estrogens or estrogens plus progestagen, 153 that did not receive any HT (38–85 years), and 155 premenopausal women (18–52 years). Polymorphisms in UGT1A1 (rs5839491) and SULT1A1 (rs1042028) were analysed by PCR-based methods. Adjusted lipid levels means were compared among genotypes by one-way analysis of variance, with corrections for multiple testing.

Results.?The UGT1A1*28 polymorphism was associated with total cholesterol (T-chol) (p?=?0.030; corrected p?=?0.060) and low-density lipoprotein cholesterol (LDL-C) levels (p?=?0.011, corrected p?=?0.022) in premenopausal women. The premenopausal and postmenopausal women, both carriers of SULT1A1*2/*2, had lower levels of T-chol and LDL-C means than carriers of the SULT1A1*1/*1 (p?=?0.004, corrected p?=?0.008 and 0.009, corrected p?=?0.018, respectively).

Conclusion.?The data showed the presence of an association between the UGT1A1*28/*28 and SULT1A1*2/*2 and T-chol and LDL-C levels in women with different hormonal status. No previous studies investigated the association of the polymorphisms examined in this study with lipoprotein levels in women separately by hormonal status.     

Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women

Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy–Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r²). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p?=?0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.     

Severe H1N1-infection during pregnancy

H1N1 is known to induce fulminant courses in youths and young adults. We report the case of a 24-year gravida 4 para 2 with singleton pregnancy admitted to obstetrical unit for fever up to 38°C during the 20th week of a so far uncomplicated pregnancy. Ultrasound examination and urine test was inconspicuous. Throat complaints were initially relieved during antibiotic therapy, but the patient developed dyspnea with progressing signs of cyanosis. Intubation was necessary on the fifth day because of decreasing oxygen saturation. Coincidentally, progressive pancytopenia and increased inflammatory activity was recorded. Echocardiography, blood cultures, and bronchial lavage brought no pathological findings, but CT revealed acute respiratory distress syndrome and hepatomegaly. Recent human immunodeficiency virus, cytomegalic virus, herpes simplex virus, classical influenza and parainfluenza infections were excluded. An H1N1-infection was confirmed by PCR on the sixth day. The antiviral therapy was changed from zanamivir to oseltamivir. Extracorporeal membrane oxygenation was necessary due to insufficient oxygen saturation by mechanical ventilation. Until this time, pregnancy seemed to be unimpaired, but a sudden spontaneous expulsion of the fetus occurred on the seventh day (weight 460 g, no anomalies detectable). Curettage post abortem was not necessary. As a result of the antiviral therapy, H1N1-DNA was not detectable at day 16. Despite all endeavors, the respiratory situation could not be improved significantly; the patient additionally developed multiorgan failure during the time course and died on the 28th day of treatment. The recent case illustrates a very dangerous and imposing course of an H1N1-infection during pregnancy.