The toxicity assessment of phosmet on development, reproduction, and gene expression in Daphnia magna.

The use of pesticides to control pests, weeds, and diseases or to regulate plant growth is indispensable in agricultural production. However, the excessive use of these chemicals has led to significant concern about their potential negative impacts on health and the environment. Phosmet is one such pesticide that is commonly used on plants and animals against cold moth, aphids, mites, suckers, and fruit flies. Here, we investigated the effects of phosmet on a model organism, Daphnia magna using acute and chronic toxicity endpoints such as lethality, mobility, genotoxicity, reproduction, and gene expression. We performed survival experiments in six-well plates at seven different concentrations (0.01, 0.1, 1, 10, 25, 50, 100 µM) as well as the control in three replicates. We observed statistically significant mortality rates at 25 µM and above upon 24 h of exposure, and at 1 µM and above following 48 h of exposure. Genotoxicity analysis, reproduction assay and qPCR analysis were carried out at concentrations of 0.01 and 0.1 µM phosmet as these concentrations did not show any lethality. Comet assay showed that exposure to phosmet resulted in significant DNA damage in the cells. Interestingly, 0.1 µM phosmet produced more offspring per adult compared to the control group indicating a hormetic response. Gene expression profiles demonstrated several genes involved in different physiological pathways, including oxidative stress, detoxification, immune system, hypoxia and iron homeostasis. Taken together, our results indicate that phosmet has negative effects on Daphnia magna in a dose- and time-dependent manner and could also induce lethal and physiological toxicities to other aquatic organisms.

In Vitro, In Vivo, and In Silico Analysis of Pyraclostrobin and Cyprodinil and Their Mixture Reveal New Targets and Signaling Mechanisms.

Pyraclostrobin and cyprodinil are broad-spectrum fungicides that are used in crops to control diseases. However, they are excessively used and, as a result, end up in the environment and threaten human health and ecosystems. Hence, knowledge of their mechanisms of action is critical to revealing their environmental fate and negative effects and regulating their use. In the present study, we conducted a comprehensive study to show the adverse effects of pyraclostrobin, cyprodinil, and their mixture using zebrafish larvae and different cell lines. Several end points were investigated, including mortality, development, gene expression, reporter assays, and molecular docking simulations. We found that both compounds and their mixture caused developmental delays and mortality in zebrafish, with a higher effect displayed by pyraclostrobin. Both compounds altered the expression of genes involved in several signaling pathways, including oxidative stress and mitochondrial function, lipid and drug metabolisms, the cell cycle, DNA damage, apoptosis, and inflammation. A noteworthy result of this study is that cyprodinil and the mixture group acted as NFκB activators, while pyraclostrobin demonstrated antagonist activity. The AHR activity was also upregulated by cyprodinil and the mixture group; however, pyraclostrobin did not show any effect. For the first time, we also demonstrated that pyraclostrobin had androgen receptor antagonist activity.

Comparative analysis of diisononyl phthalate and di(isononyl)cyclohexane-1,2 dicarboxylate plasticizers in regulation of lipid metabolism in 3T3-L1 cells.

Diisononyl phthalate (DINP) and di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) are plasticizers introduced to replace previously used phthalate plasticizers in polymeric products. Exposure to DINP and DINCH has been shown to impact lipid metabolism. However, there are limited studies that address the mechanisms of toxicity of these two plasticizers. Here, a comparative toxicity analysis has been performed to evaluate the impacts of DINP and DINCH on 3T3-L1 cells. The preadipocyte 3T3-L1 cells were exposed to 1, 10, and 100 µM of DINP or DINCH for 10 days and assessed for lipid accumulation, gene expression, and protein analysis. Lipid staining showed that higher concentrations of DINP and DINCH can induce adipogenesis. The gene expression analysis demonstrated that both DINP and DINCH could alter the expression of lipid-related genes involved in adipogenesis. DINP and DINCH upregulated Pparγ, Pparα, C/EBPα Fabp4, and Fabp5, while both compounds significantly downregulated Fasn and Gata2. Protein analysis showed that both DINP and DINCH repressed the expression of FASN. Additionally, we analyzed an independent transcriptome dataset encompassing temporal data on lipid differentiation within 3T3-L1 cells. Subsequently, we derived a gene set that accurately portrays significant pathways involved in lipid differentiation, which we subsequently subjected to experimental validation through quantitative polymerase chain reaction. In addition, we extended our analysis to encompass a thorough assessment of the expression profiles of this identical gene set across 40 discrete transcriptome datasets that have linked to diverse pathological conditions to foreseen any potential association with DINP and DINCH exposure. Comparative analysis indicated that DINP could be more effective in regulating lipid metabolism.

Sex-specific differences in zebrafish brains.

In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases.

Plasticizers: negative impacts on the thyroid hormone system.

This review aims to understand the impacts of plasticizers on the thyroid system of animals and humans. The thyroid gland is one of the earliest endocrine glands that appear during embryogenesis. The thyroid gland synthesizes thyroid hormones (TH), triiodothyronine (T3), and thyroxine (T4) that are important in the regulation of body homeostasis. TH plays critical roles in regulating different physiological functions, including metabolism, cell growth, circadian rhythm, and nervous system development. Alteration in thyroid function can lead to different medical problems. In recent years, thyroid-related medical problems have increased and this could be due to rising environmental pollutants. Plasticizers are one such group of a pollutant that impacts thyroid function. Plasticizers are man-made chemicals used in a wide range of products, such as children's toys, food packaging items, building materials, medical devices, cosmetics, and ink. The increased use of plasticizers has resulted in their detection in the environment, animals, and humans. Studies indicated that plasticizers could alter thyroid function in both animals and humans at different levels. Several studies demonstrated a positive and/or negative correlation between plasticizers and serum T4 and T3 levels. Plasticizers could also change the expression of various TH-related genes and proteins, including thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), and transporters. Histological analyses demonstrated thyroid follicular cell hypertrophy and hyperplasia in response to several plasticizers. In conclusion, plasticizers could disrupt TH homeostasis and the mechanisms of toxicity could be diverse.

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae.

Plasticizers are commonly used in different consumer goods and personal care products to provide flexibility, durability and elasticity to polymers. Due to their reported toxicity, the use of several plasticizers, including phthalates has been regulated and/or banned from the market. Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is an alternative plasticizer that was introduced to replace toxic plasticizers. Increasing global demand and lack of toxicity data and safety assessment of DINCH have raised the concern to human and animal health. Hence, in the present study, we investigated the adverse effects of DINCH (at concentrations ranging from 0.01 to 10 µM) in early developmental stages of zebrafish using different endpoints such as hatching rate, developmental abnormalities, lipid content, behavior analysis and gene expression. We found that DINCH caused hatching delay in a dose-dependent manner and altered the expression of genes involved in stress response. Lipid staining using Oil Red O stain showed a slight lipid accumulation around the yolk, brain, eye and neck with increasing concentration. Genes associated with lipid transport such as fatty acid synthesis, ß-oxidation, elongation, lipid transport were significantly altered by DINCH. Genes involved in cholesterol biosynthesis and homeostasis were also affected by DINCH indicating possible developmental neurotoxicity. Behavioral analysis of larvae demonstrated a distinct locomotor activity upon exposure to DINCH. The present data shows that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, further analyses and environmental monitoring of DINCH should be conducted to determine its safety and toxicity levels.

In silico and in vitro assessment of androgen receptor antagonists.

There is a growing concern for male reproductive health as studies suggest that there is a sharp increase in prostate cancer and other fertility related problems. Apart from lifestyle, pollutants are also known to negatively affect the reproductive system. In addition to many other compounds that have been shown to alter androgen signaling, several environmental pollutants are known to disrupt androgen signaling via binding to androgen receptor (AR) or indirectly affecting the androgen synthesis. We analyzed here the molecular mechanism of the interaction between the human AR Ligand Binding Domain (hAR-LBD) and two environmental pollutants, linuron (a herbicide) and procymidone (a pesticide), and compared with the steroid agonist dihydrotestosterone (DHT) and well-known hAR antagonists bicalutamide and enzalutamide. Using molecular docking and dynamics simulations, we showed that the co-activator interaction site of the hAR-LBD is disrupted in different ways by different ligands. Binding free energies of the ligands were also ordered in increasing order as follows: linuron, procymidone, DHT, bicalutamide, and enzalutamide. These data were confirmed by in vitro assays. Reporter assay with MDA-kb2 cells showed that linuron, procymidone, bicalutamide and enzalutamide can inhibit androgen mediated activation of luciferase activity. Gene expression analysis further showed that these compounds can inhibit the expression of prostate specific antigen (PSA) and microseminoprotein beta (MSMB) in prostate cell line LNCaP. Comparative analysis showed that procymidone is more potent than linuron in inhibiting AR activity. Furthermore, procymidone at 10 µM dose showed equivalent and higher activity to AR inhibitor enzalutamide and bicalutamide respectively.

The brominated flame retardants TBECH and DPTE alter prostate growth, histology and gene expression patterns in the mouse.

The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). in vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and ß, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated mice were used to study the androgenic effects of TBECHαß and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαß affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαß group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function.

Transcriptomic analysis of nonylphenol effect on Saccharomyces cerevisiae.

Nonylphenol (NP) is a bioaccumulative environmental estrogen that is widely used as a nonionic surfactant. We have previously examined short-term effects of NP on yeast cells using microarray technology. In the present study, we investigated the adaptive response of Saccharomyces cerevisiae BY4742 cells to NP exposure by analyzing genome-wide transcriptional profiles using RNA-sequencing. We used 2 mg/L NP concentration for 40 days of exposure. Gene expression analysis showed that a total of 948 genes were differentially expressed. Of these, 834 genes were downregulated, while 114 genes were significantly upregulated. GO enrichment analysis revealed that 369 GO terms were significantly affected by NP exposure. Further analysis showed that many of the differentially expressed genes were associated with oxidative phosphorylation, iron and copper acquisition, autophagy, pleiotropic drug resistance and cell cycle progression related processes such as DNA and mismatch repair, chromosome segregation, spindle checkpoint activity, and kinetochore organization. Overall, these results provide considerable information and a comprehensive understanding of the adaptive response to NP exposure at the gene expression level.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause male-biased sex differentiation in zebrafish.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used pharmaceuticals to treat pain, fever and inflammation. NSAIDs are also known to have many side effects including adverse effects on reproduction in both humans and animals. As NSAIDs usage is not regulated they are frequently detected at high concentrations in the environment. In order to understand the effect of NSAIDs on zebrafish sex differentiation, we used seven different NSAIDs which were either Cox-1 selective, Cox-1 biased, non-selective or COX-2 selective. We show that at higher concentration, NSAIDs are toxic to zebrafish embryo as they lead to mortality and hatching delay. Gene expression analysis following short term exposure of NSAIDs led to downregulation of female specific genes including zp2, vtg2 foxl2 and wnt4. Long term exposure of larvae to environmentally relevant concentrations of Cox-2 selective and non-selective NSAIDs resulted in male-biased sex ratio which confirmed the qRT-PCR analysis. However, the Cox-1 selective acetylsalicylic acid and the Cox-1 biased ketoprofen did not alter sex ratio. The observed male-biased sex ratio could also be due to induction of apoptosis process as the genes including p21 and casp8 were significantly upregulated following exposure to the Cox-2 selective and the non-selective NSAIDs. The present study indicates that NSAIDs alter sex differentiation in zebrafish, primarily through inhibition of Cox-2. This study clearly demonstrates that the use of NSAIDs and their release into the aquatic environment should be carefully monitored to avoid adverse effects to the aquatic organisms.

The food preservative ethoxyquin impairs zebrafish development, behavior and alters gene expression profile.

In the present study, we investigated the detrimental effects of ethoxyquin (EQ) on zebrafish embryonic development using different endpoints including lethality, malformations, locomotion and gene expression. EQ is primarily used as a preservative in animal feed and it has been shown to have negative impacts on different laboratory animals. However, studies on the adverse effects of EQ in aquatic animals are still limited. In this study, zebrafish eggs were exposed to different concentrations of EQ ranging from 1 to 100 µM for six days. In the 100 µM treated groups 95 and 100% mortality was observed at 24 and 48 h, respectively. Delayed development, decreased pigmentation and pericardial edema were observed in larvae. Behavioral analysis of larvae demonstrated a distinct locomotive pattern in response to EQ both in light and dark indicating a possible developmental neurotoxicity and deficits in locomotion. The expression levels of genes involved in several physiological pathways including stress response, cell cycle and DNA damage were altered by EQ. Our results demonstrate that EQ could cause developmental and physiological toxicity to aquatic organisms. Hence, its toxic effect should be further analyzed and its use and levels in the environment must be monitored carefully.

Comparative transcriptional analysis of methylparaben and propylparaben in zebrafish.

Parabens are widely used as preservatives in different commercial items including food, cosmetics and pharmaceuticals, and their wide use has resulted in accumulation in the environment. Parabens have been shown to have negative effects on animals as well as human health. In this study, we carried out a comprehensive study to determine the adverse effects associated with propylparaben (PP) and methylparaben (MP) on early developmental stages of zebrafish. Mortality, hatching, developmental abnormalities and gene expression profiles were investigated in embryos exposed to both compounds. The semi-static exposure conditions showed that both MP (≥100 µM) and PP (≥10 µM) are toxic to the embryos in a concentration-dependent manner and lead to developmental abnormality. Malformations such as spinal defects, pericardial edema, and pigmentation defects were observed following both MP and PP treatments. Hatching delay, mortality and developmental abnormality data indicate that PP is more toxic than MP. For gene expression analysis, 1 and 10 µM doses of MP and PP were analyzed. Genes from physiological pathways including stress response, cell cycle and DNA damage, inflammation, fatty acid metabolism and endocrine functions were affected by MP and PP. The gene expression profiles show that parabens cause toxicity by inducing oxidative stress, DNA double-strand breaks, apoptosis as well as by altering fatty acid metabolism. Altered expression of androgen receptor (ar) and estrogen receptor 2 alpha (esr2a) indicates an antiandrogenic and estrogenic activity of parabens in zebrafish. Overall, the present study provides considerable information on the negative effects of MP and PP using physiological endpoints and motivates further studies to explore the molecular mechanism of the toxicity associated with parabens.

Systems biomarkers in psoriasis: Integrative evaluation of computational and experimental data at transcript and protein levels.

Psoriasis is a complex autoimmune disease with multiple genes and proteins being involved in its pathogenesis. Despite the efforts performed to understand mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic targets, disease-specific and effective biomarkers were still not available. This study is compiled regarding clinical validation of computationally proposed biomarkers at gene and protein expression levels through qRT-PCR and ELISA techniques using skin biopsies and blood plasma. We identified several gene and protein clusters as systems biomarkers and presented the importance of gender difference in psoriasis. A gene cluster comprising of PI3, IRF9, IFIT1 and NMI were found as positively correlated and differentially co-expressed for women, whereas SUB1 gene was also included in this cluster for men. The differential expressions of IRF9 and NMI in women and SUB1 in men were validated at gene expression level via qRT-PCR. At protein level, PI3 was abundance in disease states of both genders, whereas PC4 protein and WIF1 protein were significantly higher in healthy states than disease states of male group and female group, respectively. Regarding abundancy of PI3 and WIF1 proteins in women, and PI3 and PC4 in men may be assumed as systems biomarkers at protein level.

Genome reprogramming in Saccharomyces cerevisiae upon nonylphenol exposure.

Bioaccumulative environmental estrogen, nonylphenol (NP; 4-nonylphenol), is widely used as a nonionic surfactant and can affect human health. Since genomes of Saccharomyces cerevisiae and higher eukaryotes share many structural and functional similarities, we investigated subcellular effects of NP on S. cerevisiae BY4742 cells by analyzing genome-wide transcriptional profiles. We examined effects of low (1 mg/l; <15% cell number reduction) and high (5 mg/l; >65% cell number reduction) inhibitory concentration exposures for 120 or 180 min. After 120 and 180 min of 1 mg/l NP exposure, 187 (63 downregulated, 124 upregulated) and 103 genes (56 downregulated, 47 upregulated), respectively, were differentially expressed. Similarly, 678 (168 repressed, 510 induced) and 688 genes (215 repressed, 473 induced) were differentially expressed in cells exposed to 5 mg/l NP for 120 and 180 min, respectively. Only 15 downregulated and 63 upregulated genes were common between low and high NP inhibitory concentration exposure for 120 min, whereas 16 downregulated and 31 upregulated genes were common after the 180-min exposure. Several processes/pathways were prominently affected by either low or high inhibitory concentration exposure, while certain processes were affected by both inhibitory concentrations, including ion transport, response to chemicals, transmembrane transport, cellular amino acids, and carbohydrate metabolism. While minimal expression changes were observed with low inhibitory concentration exposure, 5 mg/l NP treatment induced substantial expression changes in genes involved in oxidative phosphorylation, cell wall biogenesis, ribosomal biogenesis, and RNA processing, and encoding heat shock proteins and ubiquitin-conjugating enzymes. Collectively, these results provide considerable information on effects of NP at the molecular level.

Analysis of transcriptional profiles of Saccharomyces cerevisiae exposed to bisphenol A.

Bisphenol A (BPA), an endocrine disrupting chemical, is used as a monomer in the production of epoxy resins and polycarbonates, and as a plasticizer in polyvinyl chloride. As such, it is produced in large quantities worldwide and continuously leaches into the environment. To capture the genome reprogramming in eukaryotic cells under BPA exposure, here, we used Saccharomyces cerevisiae as model organism and analyzed the genome-wide transcriptional profiles of S. cerevisiae BY4742 in response to BPA, focusing on two exposure scenarios: (1) exposure to a low inhibition concentration (50 mg/L; resulting in <10 % inhibition in cell number) and (2) a high inhibition concentration (300 mg/L; resulting in >70 % inhibition in cell number). Based on the transcriptional profiling analyses, 81 genes were repressed and 104 genes were induced in response to 50 mg/L BPA. Meanwhile, 378 genes were downregulated and 606 genes were significantly upregulated upon exposure to 300 mg/L BPA. While similar processes were affected by exposure to distinct BPA concentrations, including mitochondrial processes, nucleobase-containing small molecule metabolic processes, transcription from the RNA polymerase II promoter, and mitosis and associated processes, the number and magnitude of differentially expressed genes differ between low and high inhibition concentration treatments. For example, exposure to 300 mg/L BPA resulted in severe changes in the expression levels of several genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, ribosomal activity, replication, and chemical responses. Conversely, only slight changes were observed in the expression of genes involved in these processes in cells exposed to 50 mg/L BPA. These results demonstrate that yeast cells respond to BPA in a concentration-dependent manner at the transcriptional level via different genes and provide insight into the molecular mechanisms underlying the modes of action of BPA.

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma.

OBJECTIVES: Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma. MATERIALS AND METHODS: In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes. RESULTS: Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk. CONCLUSION: Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.

Studies on angiotensin-converting enzyme insertion/deletion polymorphism and genotype distributions in Turkish preeclampsia patients.

Placental, immune and genetic factors are thought to play an important role in preeclampia (PE)'s pathophysiology. Angiotensin-Converting Enzyme (ACE) plays a vital role in the renin-angiotensin-system (RAS) which regulates blood pressure by converting angiotensin I into a powerfull vasoconstrictor angiotensin II. A deletion polymorphism (D allele) has been reported to be associated with elevated ACE activity. The aim of the this study was to investigate whether there is an association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and PE. In this study, 120 preeclamptic and 116 normotensive Turkish pregnant women were genotyped for ACE I/D polymorphism and the distribution of genotype and allele frequencies of this polymorphism in preeclampsia and controls were evaluated. Codominant, dominant and recessive models were appplied in ACE gene I/D polymorphism. In the codominant model, DD genotype was found significantly more frequent in preeclampsia than controls (P = 0.016). Moreover, in dominant model (DD frequency versus DI+II frequency) there was a significant relation between DD genotype and preeclampsia (P = 0.006). D allele frequency was 64.6% in preeclampsia while it was 56.1% in controls (P = 0.062). In conclusion, there was significant difference in genotype distribution between preeclampsia and controls.