Purpose The purpose of this study was to evaluate the associations between polymorphisms in vitamin D receptor (VDR), parathyroid hormone (PTH), calcium sensing receptor (CASR), insulin receptor (INSR), and adiponectin (ADIPOQ) genes and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Methods Serum levels of LH, FSH, estradiol, testosterone, prolactin, SHBG, glucose, IGF-1, IGFBP-1, calcium, phosphorus, PTH, 25(OH)D, and 1,25(OH) 2 D were measured in 56 women with PCOS. Furthermore, genotyping five, one, one, two, and two polymorphisms of the VDR, PTH, CASR, INSR, and ADIPOQ genes, respectively, were performed.Results The VDR TaqI "CC" genotype was associated with elevated serum levels of LH (p=0.011). There were significant associations between decreased levels of SHBG and both VDR BsmI "GG" (p=0.009) and ADIPOQ BsmI "CC" (p=0.016) genotypes. Furthermore, patients with CaSR Hin1I "TG" genotype showed higher HoMA-IR (p=0.008). All these associations remained significant after Bonferroni correction. In addition, phosphorus correlated negatively with estradiol (r=−0.298, P=0.026) and positively with glucose (r=0.287, P=0.032). Conclusions These data indicated for the first time that it is possible that the VDR and CASR gene variants through their effects on LH and SHBG levels, and insulin resistance are involved in pathogenesis of PCOS.

The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time-and resource-intensive process.aptamer | SELEX | evolutionary dynamics | stochastic process | hybrid model

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 "TT" genotype compared with "TG and GG" genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20-3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03-2.86). Furthermore, the ADIPOQ rs2241766 "T" allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18-2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 "TT" genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.

Our results provide evidence diagnosing that the Leu/Leu genotype of EXO1 showed an inverse association with CRC. In addition, despite other investigations, we could define a significant association between the Leu allele and CRC (p = 0.001).

SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein is a known antagonist of the transforming growth factor beta (TGF-b) signaling pathway which is involved in tumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigate the influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological features in an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthy controls were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs2337107and the risk of colorectal cancer. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). Although there was not any association between genotypes and disorder, CT was the most common genotype in this population. This genotype prevalence was also higher in the patients with well grade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not a potential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population, and suggests the need of a large-scale case-control study to validate our results.