Association of vitamin D receptor gene polymorphism with the occurrence of low bone density, osteopenia, and osteoporosis in patients with type 2 diabetes.

PURPOSE: This study aims to analyze the association between VDR gene polymorphism and the occurrence of "low bone density (LBD)/osteopenia/osteoporosis" or LBDOO in type 2 diabetes (T2D) patients among a clustered population in northwest of Iran. The studied VDR gene polymorphism included ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), EcoRV (rs4516035) and, TaqI (rs731236). METHODS: In this population-based cross-sectional study, patients with T2D were identified within a group of 1266 participants based on self-report of diabetes, history of diabetes medication, and recorded laboratory data. Separately for each polymorphism and gender, crude and adjusted (age, BMI) odds ratios (ORs) were calculated for participants with T2D through logistic regression analysis. RESULTS: The prevalence of T2D was 16.41% in people residing in the city of Sanandaj in 2011. Of the participants with T2D, 13.92% and 81.29% had osteoporosis and vitamin D deficiency, respectively. In women, the tt genotype of the TaqI gene significantly decreased the risk of LBDOO versus the Tt genotype, after adjusting for BMI and age (adjusted OR:0.18, CI95%: 0.03-0.97). Conversely, the EE genotype of the EcoRV gene enhanced the risk of LBDOO versus the Ee genotype (adjusted OR:7.64, CI95%: 2.03-28.72). CONCLUSION: The polymorphism of both TaqI and EcoRV genes was associated with the risk of LBDOO in women with T2D. This is the first time a study has highlighted this effect for the polymorphism of the EcoRV gene; we believe that this study would serve as a basis for future studies.

Comparison of Long-Acting G-CSF (PD-Lasta) with Short-Acting G-CSF (PD-Grastim) in Neutrophil Recovery Following Consolidation Chemotherapy with High-Dose Cytarabine in Acute Myeloid Leukemia: A Randomized Clinical Trial.

Background: Acute myeloid leukemia (AML) patients are often neutropenic as a result of their disease alone or following their chemotherapy. In this randomized clinical trial the efficacy of Iranian short-acting (PD-Grastim) and long-acting G-CSF (PD-Lasta) were compared in term of time to recovery from neutropenia in de novo AML patients following the consolidation chemotherapy. Materials and Methods: Patients (n = 51) received one or two courses of Cytarabine and Daunorubicin as an induction. If complete remission was achieved, the treatment was followed by high-dose Cytarabine as consolidation chemotherapy. Twenty- four hours after the consolidation chemotherapy, patient were randomized to receive either daily short-acting G-CSF (PD-Grastim) (300 µg/kg) or single-dose long-acting G-CSF (PD-Lasta) (6 mg). Results: The median time to recovery of neutrophils was 11.00 and 13.00 days for short-acting G-CSF (PD-Grastim) (n=22) and long-acting G-CSF (PD-Lasta) (n=29) groups, respectively (U=186.5, P>0.05 two-tailed). Incidence of adverse effects was similar in both short-acting G-CSF (PD-Grastim) and long-acting G-CSF (PD-Lasta) groups. Conclusion: Overall, data show that Iranian long-acting G-CSF (PD-Lasta) was not significantly different with Iranian short-acting G-CSF (PD-Grastim).

Haplotypes in vitamin D receptor gene encode risk in diabetic nephropathy.

BACKGROUND: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes and its early diagnosis can improve patient's quality of life. Genetic factors may increase the risk of DN development. This study aimed to evaluate the association of vitamin D receptor (VDR) gene polymorphisms and DN. METHOD: A total of 313 Iranian participants including 104 diabetic patients with nephropathy (DN), 100 diabetic patients without nephropathy (D) and 109 healthy people (HC) were studied. The frequencies of rs7975232, rs731236 and rs4516035 variants of VDR gene were determined and compared between three groups. Estimated haplotype frequencies between polymorphisms in the cases and controls were also calculated. RESULTS: No significant differences were identified for allele /genotype frequencies in HC, D and DN groups. However haplotype analysis showed that haplotype encompassing CCC alleles for rs7975232, rs731236 and rs4516035 variants, respectively was more frequent in DN subjects compared to HC (p-value = 0.01) and also, haplotype comprising TCC alleles was more frequent in DN group compared to both HC and D groups (p-value = 0.004 and 0.007, respectively). CONCLUSION: Our study identified that CCC and TCC VDR haplotypes are risk factors for DN in patients with diabetes type 2.

A Double-Blind, Randomized Comparison Study between Zytux™ vs MabThera® in Treatment of CLL with FCR Regimen: Non-Inferiority Clinical Trial.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux™ in comparison to MabThera® in treatment of CLL. MATERIALS AND METHODS: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux™, and group B was treated with MabThera®. A non-inferiority margin of 20% for the primary outcome was defined to examine the similarity between Zytux™ and MabThera®. RESULTS: Baseline demographic characteristics showed no statistically significant difference between the two groups. The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux™ demonstrated a similar profile of adverse reactions in comparison to MabThera®. Moreover, the overall response rate was 88% and 89% for Zytux™ and MabThera®, respectively (CI -0.17, 0.18). CONCLUSION: Results showed non-inferiority of Zytux™ in terms of efficacy and adverse events as a biosimilar version of MabThera®.

A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.

Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.