Association of rs5051 and rs699 polymorphisms in angiotensinogen with coronary artery disease in Iranian population: A case-control study.

Coronary artery disease (CAD) is the third most common cause of mortality globally (with 17.8 million deaths annually). Angiotensinogen (AGT) and polymorphisms in this gene can be considered as susceptibility factors for CAD. We performed a retrospective case-control study to determine the correlation of AGT rs5051 and rs699 polymorphisms with CAD in an Iranian population. We genotyped 310 CAD patients and 310 healthy subjects using polymerase chain reaction-based methods. To confirm the accuracy of the screening approach, 10% of genotyped subjects were validated using gold-standard Sanger Sequencing. To evaluate the effect of the candidate polymorphisms, white blood cells were randomly purified from the subjects and AGT expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Sex stratification indicated a significant correlation between CAD and male sex (P = .0101). We found a significant association between the rs5051 A allele (P = .002) and the rs699 C allele, and CAD (P = .0122) in recessive and dominant models. Moreover, our findings showed a significant association of the haplotype, including the rs5051 A/A and rs699 T/C genotypes, with CAD (P = .0405). Finally, AGT mRNA levels were significantly decreased in patients harboring the candidate polymorphisms (P = .03). According to our findings The AGT rs5051 A and AGT rs699 C alleles are predisposing variants of CAD risk and severity in the Iranian population.

CRISPR/Cas9-mediated deletion of a GA-repeat in human GPM6B leads to disruption of neural cell differentiation from NT2 cells.

The human neuron-specific gene, GPM6B (Glycoprotein membrane 6B), is considered a key gene in neural cell functionality. This gene contains an exceptionally long and strictly monomorphic short tandem repeat (STR) of 9-repeats, (GA)9. STRs in regulatory regions, may impact on the expression of nearby genes. We used CRISPR-based tool to delete this GA-repeat in NT2 cells, and analyzed the consequence of this deletion on GPM6B expression. Subsequently, the edited cells were induced to differentiate into neural cells, using retinoic acid (RA) treatment. Deletion of the GA-repeat significantly decreased the expression of GPM6B at the RNA (p < 0.05) and protein (40%) levels. Compared to the control cells, the edited cells showed dramatic decrease of the astrocyte and neural cell markers, including GFAP (0.77-fold), TUBB3 (0.57-fold), and MAP2 (0.2-fold). Subsequent sorting of the edited cells showed an increased number of NES (p < 0.01), but a decreased number of GFAP (p < 0.001), TUBB3 (p < 0.05), and MAP2 (p < 0.01), compared to the control cells. In conclusion, CRISPR/Cas9-mediated deletion of a GA-repeat in human GPM6B, led to decreased expression of this gene, which in turn, disrupted differentiation of NT2 cells into neural cells.

Association study of M235T and A-6G polymorphisms in angiotensinogen gene with risk of developing preeclampsia in Iranian population.

OBJECTIVE: Preeclampsia (PE) is a life-threatening complication of pregnancy that accounts for 12% of all maternal deaths worldwide. The aim of this study is to investigate the relationships between the polymorphisms of angiotensinogen (AGT) gene and preeclampsia. MATERIAL AND METHODS: In this study, 240 unrelated preeclampsia patients and 178 normotensive women were examined. Genomic DNA was extracted then we assessed M235T(C/T) and A-6G polymorphisms of the AGT gene. Genotyping of M235T and A-6G polymorphisms were performed using SSP-PCR and MS-PCR, respectively. RESULTS: A significant protective association was observed between A-6G G allele, A-6G A/G heterozygote genotype (OR = 0.6, p = 0.007 and OR = 0.6, p = 0.04) against PE. Furthermore, it was shown that two copies of A-6G A allele would increase PE risk (OR: 0.62, p = 0.04). Our results did not show a significant association for M235T polymorphism and PE. However, the combinations of A-6G A/A genotype and M235T T/C genotype (OR = 0.4, p = 0.02) and also A-6G A/G genotype and M235T T/C genotype (OR = 0.5, p = 0.04) in controls represented a significant protective association against PE. CONCLUSION: According to the existence of significant correlation between two candidate polymorphisms, A-6G and M235T polymorphisms, with PE disease in our study, they may be considered as valuable factors in susceptibility to PE disease in Iranian women.

The Patients' Adherence and Adverse Drug Reactions (ADRs) which are Caused by Helicobacter pylori Eradication Regimens.

BACKGROUND: Helicobacter pylori is a major cause of upper gastrointestinal disorders. The eradication of H. pylori has been recommended for the treatment of different gastrointestinal diseases. Notwithstanding, a combination therapy is needed for Helicobacter pylori eradication, but using these medications can be the cause, the incidence risk of patients' adherence to treatment regimens reduction and probably increase risk of Adverse Drug Reactions (ADRS), so, it is seem that evaluation the out come of combination therapy is need more than the past. AIM: The aim of present study was to determine the patients' adherence to the treatment and the ADRs with five eradiation regimens. SETTING AND DESIGN: A cross sectional study was done in a well known referral clinic of gastrointestinal disorders in Tehran, Iran. METHODS AND MATERIALS: Ninety patients were evaluated the study (18 in each of the five regimens). The adherence to the treatment and the ADRs of the patients were asked during the treatment, twice, by doing telephone assays. STATISTICAL ANALYSIS USED: The data were analyzed by using the SPSS, 17 software and the statistical significance was accepted for the P values of 0.05. RESULTS: 81% of the patients had a good adherence and there was no significant difference between the types of regimens (triple or quadruple therapy) and the adherence to the treatment regimens by the patients (p=0.6). Also, we found that there was no significant relationship between the types of regimens and the sex (p=0.99), education level (p=0.99), accommodation (p=0.93), an existence of underlying disease (p=0.86) and the concurrent use other medications (p=0.93). But there was a significant relationship between the patients' age and adherence to the treatment regimens (p=0.008). The most reported ADRs belonged to gastrointestinal (GI) disorders (an abnormal taste had the most prevalence (36.6%) among the GI disorders). There was no significant relationship between the regimen type and the GI ADRs, (p=0.48). CONCLUSION: The findings of this study showed that the patients' adherence to the treatment regimens and the ADRs did not have a significant relationship with the various eradication regimens for H. pylori. It seems that the type of H. pylori eradication regimen may not be an important factor in the patients' adherence to the treatment regimens and the ADRs.