Paraoxonase 1 (PON1)-L55M among common variants in the coding region of the paraoxonase gene family may contribute to the glycemic control in type 2 diabetes

Objective: Genome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control. Methods: We performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP. A mismatch-PCR/RFLP was applied for genotyping the PON2-A148G variant. Results: The variant PON1-Q192R in males (OR = 2.55, 95CI 1.16–5.69, p = 0.023) and PON2-A148G in females (OR = 1.56, 95CI 1.00–2.44, p = 0.059) were associated with T2D. Compared with the LL genotypes of PON1-L55M, HbA1c levels were significantly lower in the LM genotypes (p = 0.01) and MM genotypes (p = 0.032) in patients. Multiple linear regression analyses showed that among the study variants only the PON1-L55M variant as an independent variable significantly associated with glycemic control. This variant significantly influenced glycemic control in patients with poor glycemic control so that it was better with the following order: LL < LM < MM. Based on gamma correlation, there was a significant inverse association between the number of M alleles of the PON1-L55M and HbA1c levels (r = −0.261, p = 0.001). Conclusions: Sex should be considered a confounding variable in association studies on the variants PON1-Q192R and PON2-A148G in T2D. Patients sharing the 55 M allele were prone to having good glycemic control. Our findings provide genetic evidence that the PON1-L55M variant may be a factor contributing to glycemic control. © 2018 Elsevier B.V

The study of relationships between β-globin gene mutations in β-thalassaemia patients, in response to hydroxyurea treatment

AbstractBackground and Purpose: β-thalassaemia is the most frequent inherited disorder in the world, especially in Iran and Mazandaran Province. It is caused by mulation in β-globin gene on chromosome 11 with more than 150 different mulations causing β-thalassaemia, has been identified in the β-globin gene to date. Hydroxyurea, is one of the drugs used in Thalassemia patient’s treatment, however, it is not effective in all patients. The mechanisms of the hydroxyuea effect in not clear yet. This study compared different β-globin gene mutations in β-thalassaemia patients who were referred to the Thalassemia Research Center in Sari in two groups, good responder and non-responder, to the hydroxyurea.Materials and Methods: This was a case-control study, comparing two groups of 30 thalassaemic patients who received hydroxyurea. Two groups were included, 30 good responders to hydroxyurea treatment (control) and 30 who did not respond to the treatment (case). First, DNA was extracted from peripheral blood. Then, two different methods for mutation detection were used. In the Thalassaemia Research Center in Sari, mutations in 60 patients were identified using ARMS-PCR. Also the results were confirmed in Genetic laboratory of Amirkola, using two mutation detection methods, reverse-dot blot hybridization and ARMS-PCR.Results: In the group of good responder (control), the average patient’s age were 28/1 ± 7/78 years, and the average age at the onset of blood transfusion was reported to be 8/5 ± 8/56 year. In this group, the mean comparison of the hemoglobin level and red blood size (MCV) prior and after drug consumption were statistically significant. In the group of non-responder (case), the mean age was 21.3 ± 6.43, the mean age starting blood transfusions was 3.3 ± 3.75, and the mean of drug consumption was 2.3 ± 0.8 months. From the mutations identified, IVSII-1G>A was the most common type in both case and control group, while of 30 of control group, 22 individuals were homozygous, and 7 individuals were heterozygous for this mutation (frequency % 42.5). For the 30 case patients, 11 individuals were homozygous, while 11 were heterozygous (frequency % 27.5). Comparison between two groups, case and control group, were statistically significance (PA mutation in good responder patients to hydroxyurea as compared to the non responder group, is significant and similar to the previous findings. Key words: β-thalassaemia, Hydroxyurea, MutationJ Mazand Univ Med Sci 2008; 18(64): 1-10 (Persian

In vitro and in vivo evaluations of three-dimensional hydroxyapatite/silk fibroin nanocomposite scaffolds

In this study, three-dimensional hydroxyapatite/silk fibroin (HAp/SF) nanocomposite scaffolds were successfully prepared through layer solvent casting combined with the freeze-drying technique for tissue engineering applications. Various SF aqueous concentrations, ranging from 2.5 to 10, were used to control the physicochemical properties of the prepared scaffolds. Biologic responses of the rat bone marrow stromal cells (rBMSCs) to the HAp/SF scaffolds were examined by culturing the cells within them. In addition, biodegradation and biocompatibility of the scaffolds were evaluated in vitro and in vivo, respectively. Among the prepared scaffolds, HAp/SF-2.5 was the most brittle sample and showed porous structure with lowest mechanical properties. The average pore diameters were 350 ± 67 and 112 ± 89 μm and decreased with the increase in the SF concentration from 5 to 10, respectively. The pores formed in the scaffolds, made up of the 5 SF, were more uniform and regular than those of the scaffolds made up of 5 and 10 SF. The HAp/SF scaffolds did not change the rBMSCs viability and were not cytotoxic compared with the control sample. The scanning electron microscopy micrographs showed that the cells migrated into the pores and well attached to the scaffolds and their cytoplasm was extended in all directions, indicating a promising cell adhesion, high biocompatibility, and no cytotoxicity of the HAp/SF-5 nanocomposite scaffolds. Subcutaneous implantation of the HAp/SF-5 scaffolds in rat models suggested an excellent biocompatibility. All data obtained from this study suggest the potential use of the HAp/SF-5 for hard tissue engineering. © 2014 International Union of Biochemistry and Molecular Biology, Inc