Investigation of circadian rhythm gene Per3 in diabetic neuropathy.

PURPOSE: Diabetic neuropathy (DN) is a serious complication of diabetes that affects peripheral and autonomic nerves, and it has been linked to irregularities in circadian rhythm. Several studies have demonstrated that disruptions in circadian rhythm and changes in expression of rhythm genes may play a role in the development and progression of diabetes, including the development of DN. METHODS: In this study, the association between the VNTR polymorphism of the PER3 gene and diabetic neuropathy was investigated. The study included 84 patients with diabetes, 220 patients with diabetic neuropathy, and 218 healthy individuals as the control group. RESULTS: Upon analyzing the data from the study, it was found that there was no significant difference in the PER3 VNTR polymorphism between the diabetic neuropathy patients, diabetes and control groups. However, there was a significant difference observed between the control group and the diabetes group, particularly in terms of the 5/5 genotype and 5 alleles. Moreover, a significant difference was observed between the patient group and the control group (p < 0.05). CONCLUSIONS: In conclusion, first in the world, the relationship between PER3 gene VNTR polymorphism and diabetic neuropathy and diabetes, was investigated. Our results showed that PER3 may be associated with diabetes but not with diabetic neuropathy.

The Association of Flow-Mediated Dilatation and Blood Parameters in Primary Raynaud's Phenomenon.

Introduction: Raynaud's phenomenon (RP) is a multifactorial disorder. If any underlying disease cannot be determined to be responsible for RP, then it is considered to be the primary RP (pRP). We aimed to investigate the differences between laboratory markers and impaired endothelial function in pRP. Materials and Methods: Forty-two pRP patients and 30 healthy individuals were included as the study and control groups, respectively. The endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery. The blood samples were obtained from both groups, and white blood cell (WBC), hemoglobin, platelets, mean platelet volume (MPV), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), D-dimer, fibrinogen, albumin, fibrinogen-to-albumin ratio (FAR), neutrophil-to-lymphocyte ratio (NLR), D-dimer-to-albumin ratio (DDAR), and monocyte chemoattractant protein-1 (MCP-1) parameters were studied. The blood parameters and FMD values obtained were compared between groups. Results: The groups were similar in regard to age, gender, and smoking history (p < 0.05). There was no difference between the two groups in regard to hemoglobin, platelet, MPV, creatinine, ALT, D-dimer, albumin, FAR, NLR, and DDAR levels (p < 0.05). AST levels were slightly higher in the pRP group (p=0.027). Markedly increased WBC, fibrinogen, MPV, and MCP-1 values were detected in the pRP group (p=0.001), as well as higher abnormal FMD responses (p=0.001). There was a direct correlation between abnormal FMD response and serum MCP-1 values in patients with pRP (R: 0.308, R 2: 0.095, p: 0.044). Conclusion: It seems to be that MCP-1 levels are higher in patients with pRP, and increased values of MCP-1 levels seem to be related to impaired endothelial functions.

Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study was to evaluate whether the VNTR intron 4b/4a variant in the eNOS gene is associated with type 2 diabetes mellitus (T2DM) and DPN. METHODS: A total of 598 subjects were enrolled in the study. eNOS VNTR 4b/4a variant was genotyped by polymerase chain reaction (PCR) method. RESULTS: eNOS VNTR intron 4b/4b genotype and b allele increased in patients with both DPN and T2DM compared healthy controls (p=0.0005, OR:1.94, p= 0.000002, OR:4.10, respectively). 4a/4b genotype was more prevalent in controls than in DPN and T2DM patients (p=0.00008, OR:0.46; p=0.000004, OR:0.24, respectively). eNOS VNTR b allele was more common in DPN patients and T2DM patients compared with controls (p=0.007, p=0.00002, respectively). CONCLUSION: The eNOS VNTR "4b/4b" homozygous genotype and hence "4b"allele as a genetic risk factor for T2DM and DPN, which may serve as a useful marker of increased susceptibility to the risk of these disorders.

Prevalence of Nonalcoholic Fatty Liver Disease in Familial Mediterranean Fever.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome (MetS), insulin resistance (IR) and chronic inflammation. Although familial Mediterranean fever (FMF) patients have no symptoms in the periods between attacks, their subclinical inflammation continues. The aim of the present study was to determine the NAFLD frequency in FMF patients and to evaluate their MetS, IR and lipid profiles. METHODS: The study included 54 FMF patients and 54 control subjects. The clinical and demographic characteristics of the subjects were recorded, and the patients' Pras disease severity score was calculated. IR was determined using the homeostasis model assessment (HOMA) index. MetS was diagnosed using the revised National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III). Hepatic ultrasonography was used to diagnose NAFLD. RESULTS: NAFLD was observed in 15 FMF patients (27.8%) and 14 controls (25.9%). The difference between the groups was not significant (p=0.828). Similarly, no significant difference was found between the two groups for MetS frequency and HOMA index levels. Fasting plasma glucose was significantly higher in FMF patients, whereas differences between the two groups were not significant for lipid levels and other parameters. When FMF patients with and without NAFLD were compared, no significant difference was found in Pras disease severity score, duration of the disease and daily colchicine dose. CONCLUSION: The present study showed that NAFLD frequency was not increased in FMF patients, and that patients' MetS frequency, IR and lipid profiles were not different from control subjects.

IL-1ß and IL-1Ra Variant Profiles in Turkish Patients with Diabetic Peripheral Neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of Type 2 diabetes mellitus (T2DM). This study was conducted to investigate the possible association between interleukin-1ß (IL-1ß) rs16944 /IL-1 receptor antagonist (IL-1Ra) VNTR variants and genetic susceptibility to DPN in a Turkish cohort. METHODS: A total of 200 subjects were enrolled in this study, 98 patients with DPN and 102 cases of age and sex-matched healthy controls. Genotyping was performed for all individuals using PCR-RFLP analysis. RESULTS: IL-1ß rs16944 CC genotype had a 3.20-fold increased risk for DPN (p=0.0003, OR=3.20, 95% Cl:1.72-5.96). IL-1ß rs16944 CT genotype was higher in healthy control than patients (p=0.004). IL-1ß rs16944 C allele was higher in the patient group compared to controls while T allele was lower in patients than controls (p=0.003). IL-1Ra VNTR a1/a1 and a2/a2 genotypes were lower in DPN patients while a1/a2 genotype was higher in patients (p=0.045). The patients carrying a1/T haplotype had decreased risk of DPN than control groups (p=0.004). The patients carrying a2/a2 genotype had lower HDL level (p=0.039). The subjects carrying a2/a2 genotype had higher total cholesterol level while the subjects carrying a1/a2 genotype had lower total cholesterol (p=0.026 and p=0.037, respectively). IL-1Ra a1 allele was associated with higher HDL level (p=0.041). CONCLUSION: Findings of this study indicated that the IL-1ß rs16944 and IL-1Ra VNTR variants are probably to be associated with susceptibility DPN risk in a Turkish cohort.