The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women

Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women.

Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m², to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women.

Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ² = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes.

Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.     

The role of vitamin D receptor genes (FOKI and BSMI) polymorphism in osteoporosis

ObjectiveTo evaluate the pattern of vitamin D receptor (VDR) genes polymorphism in postmenopausal Egyptian females for possible genetic role.DesignProspective cross sectional study.Participants and methodsEgyptian postmenopausal women with and without osteoporosis were diagnosed by bone mineral density measurement then were subjected to identification of VDR genes (FOKI and BSMI) polymorphism by PCR technique followed by RFLP analysis.ResultsThe frequencies of BB, Bb and bb genotypes (BSMI polymorphism) in patients were 54%, 30% and 16%, respectively. While, in controls their frequency was 5%, 10% and 85%, respectively. The BB genotype was higher in patients than in controls (P=0.001) while the bb genotype was significantly higher in controls than in patients. Regarding the FOKI polymorphism the frequencies of FF, Ff and ff genotypes among patients were 68%, 18% and 14%, respectively while their frequency in controls were 100%, 0% and 0%, respectively. Postmenopausal females carrying either B+ve or f+ve genotype were more risky to develop osteoporosis (OR of 29.75, 1.59, respectively).ConclusionThe BB genotype was higher in patients than controls and the bb genotype is a protective genotype. The FF genotype was predominant among post menopausal females and ff genotype was associated with osteoporosis. Currently, however, the mechanisms by which VDR alleles regulate BMD remain poorly understood.     

Vitamin D receptor Fok I polymorphism is associated with low bone mineral density in postmenopausal women: a meta-analysis focused on populations in Asian countries

Objective

To explore the associations between vitamin D receptor (VDR) gene polymorphisms (including Fok I, Bsm I and Apa I) and bone mineral density (BMD) in postmenopausal Asian women.

Study design

Databases of Medline, Embase and Wangfang were retrieved to identify eligible studies, with update to 1st February 2012. Standardized mean difference (SMD) and 95% confidence intervals were calculated by using fixed- or random-effect model. Best genetic comparison model was determined by using the Thakkinstian method.

Results

A total of 14 studies with 3243 healthy postmenopausal Asian women were included in this meta-analysis. Overall, pooled analyses indicated that the f allele of VDR Fok I was significantly associated with decreased BMD in the lumbar spine (ff vs. FF: SMD (95% CI): −0.87 (−1.38, −0.35); P = 0.001 for lumbar spine; −0.43 (−0.93, 0.06), P = 0.086 for femoral neck). In contrast, we did not observe overall associations between VDR Bsm I and Apa I polymorphisms and BMD in either lumbar spine or femoral neck (Bsm I bb vs. BB: SMD (95% CI): 0.61 (−1.30, 2.53), P = 0.531 for lumbar spine; Apa I aa vs. AA: SMD (95% CI): 0.66 (−0.16, 1.48), P = 0.113 for lumbar spine). When subgroup analyses were conducted according to countries, Indians carrying the VDR Fok I ff genotype were at risk of low BMD at lumbar spine (ff vs. FF: SMD (95% CI): −0.57 (−0.85, −0.29), P < 0.001). Sensitivity analyses indicated that no single study had substantial influence on all combined analyses. In addition, no publication bias was identified.

Conclusions

This meta-analysis indicated that VDR Fok I, rather than Bsm I and Apa I polymorphisms, is associated with bone mineral density in postmenopausal Asian women (especially for Indian women), and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.     

VDR FokI polymorphism and its potential role in the pathogenesis of gestational diabetes mellitus and its complications

The aim of the study is evaluating the associations of FokI vitamin D receptor (VDR) gene polymorphisms with gestational diabetes mellitus (GDM), and its relations with postpartum metabolic syndrome. In a cohort study, 303 women referred to outpatient clinic of Shariati Hospital. The VDR FokI genotypes were determined. All subjects were followed 6–12 weeks after delivery. The frequencies of Ff, FF, and ff genotypes were 30.4% (49), 63.4% (102), and 6.2% (10), respectively, in healthy pregnancies and 34.5% (49), 54.9% (78), and 10.6% (15), respectively, in GDM patients. The ff genotype was more common in GDM patients. Healthy individuals had higher frequency of F allele, suggesting that F allele may have a role in decreased incidence of GDM. Concerning the GDM risk factors, f allele had significant association with prepregnancy obesity and family history of diabetes. In postpartum follow-up, women who developed metabolic syndrome were significantly older with higher prepregnancy body mass index, had more family history of diabetes, and also their ff genotype was two fold more frequent. Our results indicate a meaningful association between FokI VDR genotypes and an increase risk of GDM in Iranian population as well as its effects on postpartum metabolic syndrome.     

Polymorphisms of the vitamin D receptor gene predict the onset of surgical menopause in Caucasian females

We tested association of four single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) with age at surgical and natural menopause in a sample of Caucasians composed of 153 women with surgical and 260 with natural menopause. A significant association was observed between age at surgical menopause and two SNPs, rs1544410 (BsmI) and rs731236 (TaqI) (p < 0.05). For rs1544410, homozygotes of the minor allele, AA, had about two-fold higher risk of surgical menopause than homozygotes of the major allele, GG (95% confidence ratio (CI) 1.09–3.82). For rs731236, the CC subjects had a greater chance of surgical menopause than the TT subjects (odds ratio = 2.01, 95% CI 1.07–3.78). Since rs1544410 and rs731236 are in strong linkage disequilibrium, the haplotypes based on these two loci were also tested. The haplotype AC was highly significantly associated with age at surgical menopause (p = 0.008). Women with this haplotype had surgical menopause on average 2.8 years earlier than non-carriers. These results reveal the potential effect of the VDR gene on ovaries and uterus, and suggest that its SNPs can be used as predictors of genetic susceptibility for early surgical menopause and respective causal health problems.     

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024?+?283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto’s thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ² was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.     

Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin D receptor FokI start codon polymorphism to bone mineral density and the occurence of osteoporosis. METHODS: We determined the vitamin D receptor FokI start codon polymorphism using polymerase chain reaction-based restriction analysis in 163 postmenopausal women in Taiwan. The vitamin D receptor gene polymorphism was detected by the restriction enzyme FokI, where the F allele indicated the absence of the cuttable site and the f allele its presence. We then related the genotypes to bone mineral density and the occurence of osteoporosis in these women. RESULTS: The allelic frequencies for 163 postmenopausal women in Taiwan were 59.2% for F and 40.8% for f in FokI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 42.3% FF, 33.7% Ff and 24% ff. The three genotypic groups differed significantly in bone mineral density at the lumbar spine (P = 0.029). Bone mineral density was highest in the Ff group and lowest in the ff group at the lumbar spine and the femoral neck. The FokI vitamin D receptor genotype showed a significant effect on the prevalence of osteoporosis in the subjects at the lumbar spine. That is, women with genotype ff had a 2.8 times greater risk for osteoporosis (P < 0.05), and those with genotype FF had a 0.8 times greater risk than women with genotype Ff. CONCLUSION: Our findings indicate that the vitamin D receptor FokI start codon polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine.     

Polymorphisms in vitamin D receptor gene,but not vitamin D levels,are associated with polycystic ovary syndrome in Brazilian women

This study aimed to investigate the association between vitamin D (VitD) levels, polymorphisms in VDR gene (ApaI, BsmI, FokI, and TaqI) and the polycystic ovary syndrome (PCOS) in a group of Brazilian women. A total of 100 patients with PCOS and 100 control women were included. The quantification of 25-hydroxyvitamin D (25(OH)D) was performed in high-performance liquid chromatography (HPLC). Polymorphisms on VDR gene were performed by PCR-RFLP. The BsmI AG genotype was more frequent in PCOS group, while the GG genotype was more frequent in the control group (p?=?.007). The frequency of the Taql CC genotype was higher in PCOS group, while the CT genotype was the most frequent in the control group (p?=?.021). Mean serum VitD levels were similar between the groups. However, there was a negative correlation between VitD levels and Ferriman-Gallwey score (p?=?.031, r?=??.260) in the PCOS group. The TaqI and BsmI polymorphisms were associated with PCOS. Moreover, VitD levels are associated with the clinical hyperandrogenism. The data suggest the role of VitD in PCOS development and its complications.     

维生素D受体基因多态性与佝偻病关系的研究

探讨维生素D受体基因多态性与维生素D缺乏性佝偻病（佝偻病）遗传易感性的关系。方法 　应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP ）分析技术检测2003年10月至2004年10月159例佝偻病患儿和78名健康儿童（对照组）VDR基因BsmⅠ位点的多态性,比较两组之间VDR基因型和基因分布。结果　 佝偻病患儿和对照组儿童的VDR基因Bsm I位点基因型分布分别为：BB（0％）,Bb（15.7％）,bb（84.3％）和BB（0％）,Bb（11.5％）,bb（88.5％）,两组 间差异无统计学意义（P >0.05）;佝偻病患儿和对照组儿童的VDR基因Bsm I位点等位基因分布分别为：B（7.9％）,b（92.1％）和B（5.8％）,b（94.2％）, 两组间差异无统计学意义（P > 0.05）。结论　VDR基因BsmⅠ酶切位点的多态性与维生素D缺乏性佝偻病的遗传易感性相关关系尚须大样本进一步确定。     

维生素D受体基因多态性与0~6岁汉族儿童骨密度关系的研究

目的研究维生素D受体基因多态性与0~6岁汉族儿童骨密度(BMD)的关系，为临床儿童低BMD的早期预防提供理论依据。 方法上海新华医院上海市儿科医学研究所2002年7月至2004年3月收集排除影响骨代谢疾病的上海地区0~6岁汉族儿童204例，进行问卷调查、体格测量；用原子吸收分光光度计测血清锌；用放射免疫法测血清25(OH)D3；用超声BMD仪测定胫骨中段骨密度；用聚合酶链反应 限制性片段长度多态性方法，分析4个限制性酶切位点(ApaI、TaqI、BsmI、FokI)的多态分布。用多因素协变量方差分析维生素D受体(VDR)基因多态性与BMD的关系。 结果多因素协方差分析消除血清25(OH)D3水平、血清锌水平、户外体育活动等因素对BMD的影响后，发现VDR基因BsmI酶切位点等位基因型和FokI酶切位点等位基因型与BMD相关，Bb基因型的BMD百分位数明显低于bb基因型，分别为2200%和4314%，差异有显著性(F=504,P<005)；ff基因型骨密度低于Ff与FF基因型，分别为2697%、3795%、5352%，差异有极显著性(F=811,P<0001)。而在Apa I、Taq I酶切位点，不同等位基因型与BMD无关(F=108、127，P>005)。 结论VDR基因在BsmI、FokI酶切位点的多态性与0~6岁汉族儿童BMD相关。     

Serum and follicular fluid levels of IGF-II,IGF-binding protein-4 and pregnancy-associated plasma protein-A in controlled ovarian hyperstimulation cycle between polycystic ovarian syndrome (PCOS) and non-PCOS women

Objective.?To investigate the difference of serum and follicular expression patterns for IGFα, IGFBP4 and PAPP-A in COH cycle between PCOS and non-PCOS women.

Methods.?COH was performed for total 30 sterile women (20 with PCOS and 10 with normal ovarian function). The serum and follicular fluid (FF)from dominant follicles levels of IGFα, IGFBP4 and PAPP-A before COH, day of hCG, and were measured using an ELISA.

Results.?The PCOS women had significantly higher day 3 serum PAPP-A, day of hCG serum IGFBP-4, and ff IGF-II levels compared to the normoovulatory subjects. Serum levels of IGF-II and IGFBP-4 in PCOS women had increased after gonadotropins stimulation, and yet PAPP-A was decreased. Within the PCOS women, day of hCG serum IGFBP-4 was strongly correlated with BMI (r?=?0.777; P?=?0.000), day of hCG IGF II (r?=??0.573, p?=?0.008), ff IGF II (r?=??0.573, p?=?0.008) and ff PAPP-A (r?=??0.461, p?=?0.041) was inversely related to diameter >16?mm follicle number and day 3 PAPP-A correlated to diameter?>16?mm follicle number (r?=?0.474; p?=?0.035).

Conclusions.?Ovarian IGF system on the gonadotropin response to differences in the PCOS and non-PCOS women in COH cycle, and may indicate a inordinate IGF system that might disturb folliculogenesis in PCOS women.     

Maternal–fetal vitamin D receptor polymorphisms significantly associated with preterm birth

Purpose

Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB.

Methods

Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24–36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn.

Results

Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183–3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p < 0.05) 1.73-fold increase of PTB. Women with history of previous (≥1) spontaneous miscarriage had a significant increased risk for PTB if their newborn carried either of the VDR BsmI homozygous (BB or bb) genotypes compared to the heterozygous (Bb) genotype [OR 6.857, (CI) 1.273–36.934, p = 0.018 and OR 9.231, (CI) 1.753–48.618, p = 0.008, respectively], or VDR ApaI homozygous (AA or aa) genotype compared to heterozygous (Aa) genotype [OR 4.33, (CI) 1.029–18.257, p = 0.046 and OR 7.2, (CI) 1.34–38.917, p = 0.021, respectively].

Conclusions

We show association between maternal and fetal VDR genotype variants with PTB.

     

Gonadotropin-releasing hormone antagonists increase follicular fluid insulin-like growth factor-I and vascular endothelial growth factor during ovarian stimulation cycles

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E₂) levels (p < 0.001 and p < 0.05, respectively), FF E₂ and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E₂ levels.     

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.     

Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis

Objective.?Pyelonephritis during pregnancy is associated with a more severe course than in the non-pregnant state. This has been attributed to an increased susceptibility of pregnant women to microbial products. The complement system is part of innate immunity and its alternative pathway is activated mainly by microorganisms. The purpose of this study was to determine if activation of the alternative pathway of the complement system (determined by maternal fragment Bb concentrations) occurs in pregnant women with acute pyelonephritis.

Methods.?This cross-sectional study included the following groups: (1) normal pregnant women (n?=?62) and (2) pregnant women with pyelonephritis (n?=?38). Maternal plasma fragment Bb concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results.?(1) Pregnant women with pyelonephritis had a higher median plasma concentration of fragment Bb than those with a normal pregnancy (1.3?μg/ml, IQR: 1.1–1.9 vs. 0.8?μg/ml, IQR: 0.7–0.9; p?<?0.001); (2) No significant differences were observed in the median maternal plasma concentration of fragment Bb between pregnant women with pyelonephritis who had a positive blood culture and those with a negative blood culture (1.4?μg/ml, IQR: 1.1–3.5 vs. 1.3?μg/ml, IQR: 1.1–1.9; p?=?0.2).

Conclusions.?Pregnant women with acute pyelonephritis have evidence of activation of the alternative pathway of the complement system, regardless of the presence or absence of a positive blood culture.     

Longitudinal changes of adiponectin,carbohydrate and lipid metabolism in pregnant women at high risk for gestational diabetes

To evaluate, in pregnant women at high risk for gestational diabetes (GDM), the longitudinal changes of adiponectin, carbohydrate and lipid metabolism, and to assess their independent value as risk factors for the development of GDM. Fifty women at beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. Twelve patients developed GDM. In both groups, GDM and normal glucose tolerance (NGT), adiponectin decreased from 1st to 2nd and 3rd trimesters by about 5 and 20% (GDM, p?<?0.05), and of about 17 and 25% in NGT (p?<?0.05), respectively. Values observed in NGT were similar to those of GDM (F?=?9.401; p?=?0.238). The Cox regression model identified as the strongest independent risk factor for GDM HOMA over 1.24 (RR?=?14.12) at 1st trimester, fasting glycaemia over 87?mg/dl (RR?=?42.68) triglycerides over 158?mg/dl (RR?=?5.87) and body mass index (BMI) over 27?kg/m² (RR?=?4.38) at 2nd trimester. Adiponectin in high-risk women is characterised by a constant reduction throughout gestation, irrespective of the development of GDM. HOMA, fasting glycaemia, triglycerides and BMI, but not adiponectin are independent predictors of GDM.     

CFTR and FOXO1 gene expression are reduced and high mobility group box 1 (HMGB1) is increased in the ovaries and serum of women with polycystic ovarian syndrome

Abstract

We previously described increased HMGB1 and reduced FOXO1 dependent on CFTR loss of function in cystic fibrosis (CF) and we showed in vitro that HMGB1 was lowered by insulin. Reduced CFTR gene expression has been described in granulosa cells (GC) from PCOS-induced rats. We aimed at studying CFTR and FOXO1 gene expression in GC, HMGB1 concentrations in serum and follicular fluids (FF), and insulin and IL-6 in FF in PCOS women. Thirty PCOS and 36 non-PCOS women (CTRL) undergoing in vitro fertilization were enrolled. CFTR and FOXO1 gene expression were downregulated in PCOS (p?≤?.05). HMGB1 was higher in PCOS both in FF (p?≤?.05) and in serum (p?<?.005) whereas insulin was lower, and IL-6 was unchanged with respect to controls. 17-β estradiol was higher in PCOS than in CTRL (p?≤?.005). HMGB1 correlated negatively with insulin in FF (p?≤?.005). The increase in HMGB1 both in FF and in serum, likely reflects both low grade inflammation and insulin sensitivity. IL-6 was unchanged possibly reflecting functions other than inflammation.     

A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome

Objective: To compare N-acetyl cysteine (NAC) and metformin on polycystic ovary syndrome (PCOS).

Method: Study was performed as a randomized double-blind clinical trial on women with diagnosis of PCOS without additional complications. In one group, oral NAC 600?mg, three times a day and in the other group, 500?mg oral metformin, three times a day were prescribed. Duration of treatment was 24 weeks, and after finishing this period of treatment, fasting blood glucose (FBS) and insulin, lipid profile and Homeostasis Model Assessment (HOMA) index were measured (all the blood samples were taken while fasting) and were compared in the two groups.

Results: Forty-six women in NAC group and 48 women in metformin group finished the study. The two groups did not show significant difference according to age, body mass index (BMI) of more than 30; mean BMI, AUB, FBS, fasting blood insulin, lipid profile and HOMA index before treatment. After 24 weeks of treatment; BMI >30 [17 (35.4%) versus 7 (15.2%), p?=?0.033], mean BMI [(28.36?±?2.27) versus (27.11?±?3.55), p?=?0.44], number of women with the complain of abnormal uterine bleeding (AUB) [24 (50%) versus 13 (28.3%), p?=?0.037], FBS [(90.02?±?6.24) versus (86.61?±?7.81), p?=?0.021], fasting insulin (10.40?±?2.64 versus 8.89?±?2.20, p?=?0.004), HOMA Index (2.09?±?0.69 versus 1.71?±?0.45, p?=?0.001), low density lipoprotein (LDL) (141.83?±?26.98 versus 127.89?±?28.70, p?=?0.017) were less in NAC group. Triglyceride (TG) and total cholesterol did not show significant difference between the two groups after treatment. High-density lipoprotein (HDL) was higher in NAC group.

Conclusion: NAC can improve lipid profile and fasting blood sugar (FBS) and fasting blood insulin better than metformin.     

Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation

Objective.?Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm) and in the presence of intra-amniotic infection/inflammation (IAI).

Study design.?This cross-sectional study included patients in the following groups: (1) mid-trimester (n = 64); (2) term in spontaneous labor (n = 70); (3) term not in labor (n = 43); (4) spontaneous preterm labor (PTL) who delivered at term (n = 76); (5) PTL without IAI who delivered preterm (n = 73); (6) PTL with IAI (n = 76); (7) preterm prelabor rupture of membranes (PROM) without IAI (n = 71); and (8) preterm PROM with IAI (n = 71). Fragment Bb concentration in AF was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses.

Results.?(1) Fragment Bb was detected in all AF samples (n = 544); (2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/ml, interquartile range (IQR) 1.78–3.22 vs. 1.64 μg/ml, IQR 1.06–3.49; p < 0.001]; (3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI, who delivered preterm (4.82 μg/ml, IQR 3.32–6.08 vs. 3.67 μg/ml, IQR 2.35–4.57; p < 0.001) and than that of women with an episode of PTL, who delivered at term (3.21 μg/ml, IQR 2.39–4.16; p < 0.001); (4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/ml, IQR 2.58–5.79 vs. 2.79 μg/ml, IQR 2.09–3.89; p < 0.001). (5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 μg/ml, IQR 1.86–3.22; p = 0.97).

Conclusions.?(1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the AF, and its concentration increases with advancing gestational age; (2) AF concentrations of fragment Bb are higher in pregnancies complicated with IAI; and (3) labor at term is not associated with changes in the AF concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI.     

The bone mass density in postmenopausal women using hormonal replacement therapy in relation to polymorphism in vitamin D receptor and estrogen receptor genes

The aims of the study were as follows: (1) To identify the differences in spinal body mass density (BMD) in relation to polymorphism in vitamin D receptor (VDR) and estrogen receptor-α (ERα) genes in untreated women with postmenopausal osteoporosis. (2) To assess the efficacy of treatment in women with postmenopausal osteoporosis in relation to polymorphism in VDR and ERα genes. (3) To find the estradiol concentration necessary to protect bone tissue in patients with a given polymorphism in VDR and ERα genes.

Methods.?The study included 44 postmenopausal women with primary osteoporosis who used cyclic hormonal replacement therapy (HRT) for a year. The polymorphism of ERα and VDR genes were evaluated. We also determined the age, body mass index and spinal BMD before and after 12 months of administration the HRT.

Results.?We found a significant spinal BMD increase, what is connected with ERα genotype and both VDR and ERα genes. There is no such a correlation observed in polymorphism of VDR gene.

Conclusions.?(1) There is no relationship between VDR and ERα genes polymorphism and the stage of osteoporosis related to the spinal BMD value before treatment. (2) The XX, PP or Bb markers or only X, P, B alleles are connected with a significant decrease of treatment efficacy. (3) Estradiol serum concentration before and during HRT is not dependent on the polymorphism of VDR and ERα genes.