Background:We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients. Methods: The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique. Results: After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases (p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only (p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups (p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls (p = 0.001), while no difference was detected between complicated and noncomplicated cases (p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions (p = 0.7 and 0.1, respectively) and allele frequencies (p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele (p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications (p = 0.02 and 0.003, respectively). Conclusion: Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.

The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.

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BackgroundIncreased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset and progression of atherosclerosis. Recently, Paraoxonase −1 (PON1) which accounts for most of the antioxidant effect of high density lipoprotein (HDL) cholesterol has been presented as a potential therapeutic agent against atherosclerosis development. Allele frequencies for PON1 gene that influence enzyme concentration as well as activity differ greatly among ethnic groups and data from several studies showed ethnic variations in the interpretation of cardiovascular disease (CVD) associated with PON1 polymorphisms. In this work, we investigated PON1 Q192R and L55M polymorphisms in Egyptian patients with type 2 diabetes mellitus (T2DM) and its association with CVD.MethodsThe study included 184 subjects classified into 3 groups; T2DM, T2DM + CVD, and healthy controls. PON1 polymorphisms were genotyped by real-time PCR and PON1 concentration was assayed in serum by ELISA (enzyme linked immunesorbent assay).ResultsGenotype and allele frequencies of Q192R were significantly different between controls and diabetic patients. Frequency of QQ genotype was significantly higher in healthy controls, while QR and RR genotypes were significantly higher in diabetic patients (p = 0.02). Frequency of 55LL and LM genotypes were significantly higher in patients than in controls (p = 0.009). Q192R polymorphism associated with CVD in our diabetic patients (p = 0.01) and with low serum PON1 concentration (p = 0.04). Multiple logistic regression analysis revealed significant correlations between 192R and other independent CVD risk factors.ConclusionPON1 192R and 55 L alleles are associated with T2DM. Q192R polymorphism is associated with CVD and lower serum enzyme concentration and might represents a novel risk factor for CVD in Egyptian patients with T2DM.

IntroductionAdiponectin, leptin and resistin are adipokines that play important roles in the regulation of lipid and carbohydrate metabolism in type 2 diabetes (T2DM). However, their influence in type 1 diabetes mellitus is still unknown. The aim of this study was to measure serum adiponectin, leptin and resistin levels and to investigate their relationships with vitamin D and other clinical and laboratory parameters in patients with type 1 diabetes.Material and methodsFifty subjects with type 1 diabetes and 50 healthy age- and sex-matched subjects were selected from the Endocrinology Outpatient Clinic of Cairo University Pediatrics Hospital. Enzyme-linked immunosorbent assay was used to measure the levels of leptin, adiponectin and resistin. Vitamin D levels were measured using electro-chemiluminescence immunoassay.ResultsThere were no significant differences in adiponectin and leptin levels between diabetic and control subjects (p = 0.6 and p = 0.5 respectively). Resistin levels were significantly higher in the diabetic group compared to controls (p < 0.001) and in postpubertal patients compared to prepubertal patients (p < 0.04). Serum resistin in type 1 diabetes showed a negative correlation with vitamin D (p < 0.001) and a positive correlation with glycated hemoglobin (HbA1c) (p = 0.006), while other adipokines were not interrelated.ConclusionsThese results strongly support a role of resistin and vitamin D deficiency in the pathophysiology of type 1 diabetes. Vitamin D may be involved in resistin regulation through an unknown mechanism. Further studies are recommended to understand resistin regulation in type 1 diabetes.