Association of rs4784227-CASC16 (LOC643714 locus) and rs4782447-ACSF3 polymorphisms and their association with breast cancer risk among Iranian population

TOX3 and FOXA1 proteins are believed to be involved in the susceptibility of breast cancer. rs4782447 and rs4784227, as single nucleotide polymorphisms (SNPs), located at the 16q may affect the FOXA1 DNA binding sequence change and therefore may enhance the FOXA1-binding affinity to the promoter of TOX3 gene. This study aimed to investigate the association of these SNPs/haplotypes with breast cancer susceptibility in Iranian population. We conducted a case-control study of 1072 blood samples (505 breast cancer patients and 567 controls). Genotyping of rs4784227 and rs4782447 SNPs was carried out by ARMS PCR. Moreover, statistical analysis was done by SPSS 20.0 (IBM Inc., Chicago, IL, USA) and SNP analyser 2.0. There was a strongly significant statistical association between alleles and genotypes of rs4784227 with breast cancer susceptibility in a group of Iranian women (p<0.05). Moreover, a significant association was demonstrated between TA haplotype and breast cancer risk (OR=0.78; 95% CI (0.62-0.96); P-value=0.025). In this respect, although we did not observe a statistically significant association between rs4782447 with breast cancer susceptibility, the combination of the alleles of rs4784227 and rs4782447 SNPs may also affect the risk. This is in line with other studies where they suggest these SNPs as risk-associated polymorphisms by which lead to disruption of as a distal enhancer, FOXA1, binding and following that change in TOX3 expression that can eventually affect the risk of breast cancer

Association of PICK1 and BDNF variations with increased risk of methamphetamine dependence among Iranian population : a case–control study

Funding Information: This study was financially supported by the Mashhad University of Medical Sciences (Grant Number: 931681).Peer reviewedPublisher PD

A method for improving the efficiency of DNA extraction from clotted blood samples

Funding information: This study was supported by a grant from the Research Council of the Mashhad University of Medical Sciences (Grant No: 931680). The authors would like to thank Dr. Hossein Eshghi at Department of Chemistry, Faculty of Science, the Ferdowsi University of Mashhad for his assistance in the experiment and Mohammad Sadegh Khorami who contributed to this study. We are also particularly grateful to the Research Council of the Mashhad University of Medical Sciences (MUMS) for the financial support of this studyPeer reviewedPublisher PD

Evaluating the association between ccr5delta32 polymorphism (Rs333) and the risk of breast cancer in a cohort of Iranian population

Funding Information: This manuscript was supported by the Student Research Committee of Mashhad University of science (Grant Numbers: 951734 & 961689).Peer reviewedPublisher PD

The chromatin landscape of healthy and injured cell types in the human kidney

Abstract There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks

The chromatin landscape of healthy and injured cell types in the human kidney.

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidneys active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks