Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response.

Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between BMP15 and GDF9 variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of BMP15 and GDF9 were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of BMP15 and GDF9 genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32-4.11, p = 0.004).The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response.

Identification of a FAS/FASL haplotype associated with endometriosis in Iranian patients.

Risk factors for ovarian cancer include a number of genetic variants as well as endometriosis. The FAS-FASL system is one of the apoptotic pathways that play an essential role in the apoptotic process within the endometrium. Here, we evaluate the correlation between FAS-FASL polymorphisms with the risk of endometriosis in Iranian patients and healthy controls. We extracted DNA from whole blood samples using a DNA Purification Kit. Using the PCR-RFLP method, three SNPs, including FAS (-670 A/G) and FASL (-844 C/T and _124G/A) genes, were genotyped in 112 patients with endometriosis as well as 110 healthy controls. The frequency of genotypes and the alleles of these SNPs were analyzed by the chi-squared test for the significant association. Haplotype analysis was done by the PLINK software. The frequency distribution of haplotypes was significant between SNPs so that the ACG haplotype was more frequent in the cases than in the controls (p = .017). These results indicate that haplotype analysis can be useful for SNP analysis. The ACG haplotypes in FAS-670A/G, FASL-844C/T, and _124G/A genes may be correlated with the progression of endometriosis.

Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study.

BACKGROUND: Genetic factors play a substantial role in acute myeloid leukemia (AML) etiology. Overexpression of the mouse double minute 2 (MDM2) gene has been explored in many tumors. However, the role of MDM2 -309T>G (rs2279744) polymorphism in AML remains unclear. We have performed this study to examine the association of MDM2 -309T>G with AML in an Iranian population. METHODS: We have examined the association of N MDM2 -309T>G polymorphism in 73 cases diagnosed with AML and 80 healthy controls by tetra-primer amplification refractory mutation system (ARMS) PCR assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. RESULTS: The TT, GG and GG genotypes of MDM2 -309T>G polymorphism in patients were 32.9%, 23.2% and 43.9%, while in controls were 86.2%, 7.5% and 6.3%, respectively. Moreover, Frequency of mutant allele (G) was 55.6% in cases with AML and 10.0% in controls. The mutant homozygote genotype (GG) was associated with an increased susceptibility to AML (OR 1.471; 95% CI: 1.062-1.844; p=0.004). CONCLUSION: Our results showed that the MDM2 -309T>G polymorphism was significantly associated with increased risk of AML in the Iranian population. Thus, the MDM2 -309T>G polymorphism might be useful genetic susceptibility factors in the pathogenesis of AML.

Air pollution and telomere length in adults: A systematic review and meta-analysis of observational studies.

Telomere length (TL) has been suggested to be a surrogate for cellular ageing, and a record of cumulative inflammation and oxidative stress over life. An emerging body of evidence has associated exposure to air pollution to changes in TL. To date there is no available systematic review of literature on this association. We aimed to systematically review and conduct meta-analysis of published studies on the relationship between air pollution and TL in adults. Electronic databases were systematically searched for available English language studies on the association between air pollution and TL published up to 1 July 2018. Meta-analyses were conducted following MOOSE guidelines. The heterogeneity in the reported associations was assessed using Cochran's Q test and quantified as I2 index. Publication bias was assessed using Egger's regression. Our search identified 19 eligible studies including 11 retrospective and eight prospective studies of which, four had excellent quality, ten had good quality and five had fair quality. Meta-analysis result of two studies on long-term exposure to PM2.5 showed an inverse association between these exposures and TL (for 5 µg/m3 PM2.5-0.03 95% CI; -0.05, -0.01). Meta-analysis of short-term exposure to PM2.5 with three studies and Polychlorinated Biphenyls (PCBs) with two studies revealed a direct association between these exposures and TL (0.03 95% CI; 0.02, 0.04 and 0.10 95% CI; 0.06, 0.15 respectively). No statistically significant relationship between exposure to PM10 and polycyclic aromatic hydrocarbons (PAHs) exposure and TL were observed. We observed suggestive evidence for associations between air pollution and TL with potentially different direction of associations for short- and long-term exposures.

Mortality and morbidity due to exposure to ambient particulate matter.

The aim of this study was to investigate spatial variation and health risk of the exposure to PM2.5 (particulate matter with a diameter of 2.5 µm or less) and PM10 (particulate matter with a diameter of 10 µm or less) in Sabzevar, Iran. PM2.5 and PM10 were measured during three campaigns from April to November 2017, in 26 sampling points. Spatial analysis was performed using kriging and autocorrelations (Moran's index) model in Arc GIS software. Relationship between exposure to the PM2.5 and PM10 and their health impacts were investigated by AirQ 2.2.3 software. The mean concentrations (and standard deviation) of PM 2.5 and PM10 over the entire study period were 32.54 (37.28) and 42.61 (47.76) µg/m3, respectively, which were higher than the guideline of World Health Organization. According to the spatial analysis, the maximum concentrations of PM2.5 and PM10 were around the main highway (beltway) which placed all over the south of Sabzevar. According to the Moran's index, the emission patterns for PM2.5 (Z-score = 2.53; P-value = 0.011) and PM10 (Z-score = 2.82; P-value = 0.004) were clustered. The attributable percentage (AP) of total mortality related to PM2.5 and PM10 were 3.544% (95% confidence interval (CI): 2.623-4.447%) and 2.055% (95% CI: 1.379-2.721%) per increasing each 10 µg/m3 of these pollutants, respectively. According to observed results, it is suggested that the beltway and other pollution sources, such as industries, should be placed at a greater distance from the city, to reduce PM amounts in residential areas.

Environmental determinants of polycyclic aromatic hydrocarbons exposure at home, at kindergartens and during a commute.

The aim of this study was to assess the potential health risk of exposure to polycyclic aromatic hydrocarbons (PAHs) at home and kindergarten for pre-school children. The urine samples were taken from 200 pre-school children aged 5-7 years and analyzed for 1-OHP as a biomarker of PAHs. Mixed effect models were applied to investigate the association between effective environmental parameters (mode of transport, distance to major roads, traffic density, greenness, tobacco exposure, home ventilation, and grill foods) and urinary 1-OHP levels. A Monte-Carlo simulation technique was applied to calculate the risk of exposure to PAHs and to check the uncertainty of input variables and the sensitivity of the estimated risk. The median and inter quartile range (IQR) of 1-OHP was 257 (188.5) ng L-1. There was a positive significant association between distance from the kindergartens to the green space with surface area ≥5000 m2 and 1-OHP concentration (ß = 0.844, 95% CI: 0.223, 1.46, P-value = 0.009). Also, urinary 1-OHP was found to be inversely associated with the time the window was open at the home (ß = -12.56, 95% CI: -23.52, -1.596, P-value = 0.025) and normalized difference vegetation index (NDVI) in a 100 m buffer around the homes. The mean (9.76 E-3) and 95th percentile (3.28 E-2) of the hazard quotient (HQ) indicated that the concentration of urinary 1-OHP is at a safe level for the target population (HQ < 1). According to the sensitivity analysis results, the concentration of 1-OHP is the most influential variable in the estimated risk. Our findings indicated that the proximity of homes and kindergartens to green space areas and their remoteness from the main streets and heavy traffic areas are associated with reduced exposure to PAHs.

The relationship between environmental exposures and hormonal abnormalities in pregnant women: An epidemiological study in Yazd, Iran.

PROBLEM: The process of industrialization and lifestyle changes have gradually exposed human societies to a larger number of environmental risk factors, which may cause hormonal abnormalities and congenital anomalies. BACKGROUND: The current study aimed to investigate the relationship between environmental factors and hormonal abnormalities among pregnant women in Yazd, Iran. METHODS: A hundred participants were randomly selected from among a group of pregnant women. According to the screening tests (AFP, free ß- HCG, uE3, PAPP-A, and inhibin-A) performed at the genome clinic in Yazd in 2016, the risk of Down Syndrome (DS) was sufficiently high in this group of pregnant women from which the participants were selected. A questionnaire was used to collect data on the degree of the participants' exposure to pesticides at home, use of canned and fast foods, and consumption of greenhouse fruits. The collected data were analyzed by One-way ANOVA and Kruskal-Wallis Test. FINDINGS: The mean of Multiple of Median (MoM) for inhibin-A was significantly higher among pregnant women who often or always used pesticides at home (p=0.047). The mean MoM for free ß-HCG was significantly higher among pregnant women who often or always used canned foods (p=0.024). Finally, the mean MoM for uE3 (1.85±1.30) was significantly higher among pregnant women who never consumed greenhouse fruits (p=0.003). CONCLUSION: It can be concluded that it is possible to reduce environmental exposures affecting hormonal abnormalities among pregnant women by improving nutritional patterns, minimizing the use of pesticides at home, and reducing the intake of canned foods and greenhouse fruits.

Association of SNP rs.2414096 CYP19 gene with polycystic ovarian syndrome in Iranian women.

BACKGROUND: Genetic factors are believed to play an important role in the etiology of polycystic ovarian syndrome (PCOS) which is the most common endocrinological disorder of women in their reproductive age. Androgen metabolism is impaired in PCOS and, thus, CYP19 gene which is involved in this pathway can be a candidate gene. Previous studies have shown a relationship between single nucleotide polymorphism (SNP) of CYP19 in hyperandrogenism and PCOS in some racial groups. OBJECTIVE: This study was designed to elucidate the role of CYP19 gene in PCOS in Iran. MATERIALS AND METHODS: In this case-control study, 70 PCOS women and 70 non-PCOS women as normal control were selected. Following the informed consent, 5 ml blood was taken from individuals and subsequently, genomic DNA was extracted by salting out method. Furthermore, a set of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was carried out using specific primers for SNP rs.2414096 followed by enzyme digestion, with HSP92II. RESULTS: Genotype frequencies of SNP rs. 2414096 in PCOS women were as follows: AA (14.4%), AG (44.3%), and GG (41.4%) while in normal group, genotypes were 24.3%, 52.8%, and 22.9%, respectively. Allele frequencies in PCOS group were 49.3% for A and 50.7% for G, whereas normal group had a different percentage of A (36.4%) and G (63.6%). The calculations for both genotypic and allelic frequencies showed statistical significance difference. CONCLUSION: Variants of SNP rs. 2414096 in CYP19 could play a role in the development of PCOS in Iranian women.

Anxiety leads to up-regulation of CD36 on the monocytes of chronic hepatitis B-infected patients.

Introduction It has been hypothesized that mental disorders including depression and anxiety can affect immune responses. The study was done to evaluate the relation between depression and anxiety and expression levels of CD36, CD68, and CD9 on peripheral blood monocytes of chronic hepatitis B (CHB) patients. Methods Sixty CHB patients were selected with various ranges of depression and anxiety. Depression and anxiety were evaluated using a standard questionnaire by an expert psychiatrist according to BECK's Depression Inventory II and Hamilton Anxiety Rating Scale, respectively. The levels of CD36, CD68, and CD9 on the peripheral blood monocytes have been performed using flow cytometry technique. Results The results demonstrated that levels of CD36 were significantly increased on the peripheral blood monocytes of CHB patients when compared with CHB patients with no anxiety. Expression levels of CD68 and CD9 were not significantly altered on the CHB patients with various ranges of anxiety. Expression levels of CD36, CD68, and CD9 were also not significantly altered on the CHB patients with various ranges of depression. Discussion It seems that anxiety induces inflammation in the CHB patients by induction of alteration in several molecules including up-regulation of CD36. CD36 plays important roles in the induction of tissue damage; hence, it may be hypothesized that anxiety may participate in the induction of some hepatitis B complications.

An inhibitory enzyme electrode for hydrogen sulfide detection.

An enzymatic biosensing system has been developed to study the capability of ascorbate oxidase (AOx), EC (1.10.3.3), in hydrogen sulfide (H2S) detection, based on the inhibition of AOx activity. The immobilization parameters including glutaraldehyde (GA) concentration and pH were optimized using experimental design. The optimized values of GA concentration and pH were found to be 12.5% (w/w) and 7, respectively, where the enzymatic reaction reached the steady-state level within 55 s. A linear relationship was observed between the decrease in the oxygen concentration and H2S concentration, where H2S concentration is in the range of 1-15 mg/L. Moreover, to investigate the selectivity of the biosensor, a certain H2S concentration (9 mg/L) was used against different ions. The results indicated that Fe(3+) and SO4(-2) ions had no significant (11% error) effect on the H2S detection. The operational stability of the biosensing system was determined in terms of response to H2S concentration, at optimal working conditions. The enzyme electrode could retain 73% of its original sensitivity after this period, which has made it possible for the system to measure H2S with concentrations as low as 0.5 mg/L.