Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

PURPOSE: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. METHODS: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. RESULTS: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. CONCLUSION: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

The GPx-1 Gene Variants (rs1050450) in Obesity: Association with the Risk of Obesity and the GPx Activity in Females.

Background: This study aimed to investigate the GPx-1 gene polymorphism (rs1050450), the level of oxidative stress and antioxidant parameters, and the lipid profile in an obese Kurdish population in Sulaimani, Iraq. Methods: In a case-control study,134 obese subjects and 131 normal BMI healthy individuals participated. The GPx-1 gene polymorphism was assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The levels of biochemical and oxidative parameters were determined using photometric methods. Results: The results showed that the fasting blood sugar (FBS), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in obese subjects compared to the control group. Obese individuals had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) than the controls. The GPx-1 activity and total antioxidant capacity (TAC) levels were significantly elevated in the obese group compared to the control group (P=0.006, and P<0.001, respectively). No significant difference was detected in genotype and allele frequencies of GPx-1 (rs1050450) between obese and normal BMI groups. However, the presence of the GPx-1 TT genotype enhanced the risk of obesity in females by 1.93-fold (95% CI 1.04-3.58, P=0.036). In the total population, the GPx activity increased in the presence of TT compared to CC+CT and CT genotypes. Conclusion: The study indicated that obesity is linked to significantly higher levels of FBS, TG, LDL-C, TAC, and GPx activity and lower level of HDL-C. Also, we found the GPx-1 gene polymorphism was associated with the risk of obesity in females and increased the GPx activity.

Tobacco smoking and blood parameters in the kurdish population of Iran.

OBJECTIVE: This study investigates the relationship between smoking and blood parameters in the Iranian Kurdish population. METHOD: The current study was conducted based on the recruitment phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study. RESULTS: Current smokers had higher levels of RBC count, HCT, HGB, MCV, MCH, MCHC, WBC count, and GR%, than in other groups significantly. Passive smokers had higher levels of PLT count and PCT statistically. The increasing exposure time of smoking positively affected WBC count, GR%, PLT count, PCT, and RDW in female passive smokers. In addition, heavy smokers, as well as participants with a higher duration time of smoking, had the same results for significantly lower levels of lymphocyte and monocyte and a higher level of RBC indices. CONCLUSION: According to the present study, along with the current smokers, the intensity of smoking, as well as the duration time of the smoke, could have a positive correlation with blood parameters. Furthermore, passive smokers and specifically secondhand female smokers were more vulnerable to smoke.

Association of interleukin-8 polymorphism (+ 781 C/T) with the risk of oral Lichen Planus disease.

BACKGROUND: Oral Lichen Planus (OLP) is a chronic inflammatory mucosal disease. The pathogenesis of OLP is unknown. The Single Nucleotide Polymorphism (SNP) that occurs in the regulatory position + 781 could affect the expression of interleukin-8. This polymorphism is probably associated with increased serum levels of IL-8. The current study aimed to investigate the genotype and allele frequencies of IL-8( + 781 C/T) in OLP patients and whether it is associated with the severity of OLP disease in an Iranian population. METHODS: Three milliliters of saliva were taken from 100 patients with OLP and 100 healthy individuals who were matched in age and gender. After DNA extraction from saliva samples of patients and healthy individuals, the genotype of IL-8 at position + 781 is detected using the PCR-RFLP method. The results were analyzed using SPSS software. RESULTS: Frequency of C/C, T/C, and T/T genotypes at position IL-8 + 781 gene in the patient group were 47%, 41%, and 12%, respectively, and in the control group, were 37%, 42%, and 21%. The difference between the two groups regarding allele frequency distribution was statistically significant (χ2 = 3.86, p = 0.049, 95% CI = 0.44-1, OR = 0.66). Our results indicated the significantly higher frequency of the TT genotype in the erosive OLP compared to the nonerosive group (p = 0.03, OR = 0.89, 95% CI = 0.49-1.6). CONCLUSION: This study depicted the difference in the frequency of SNP IL-8 + 781 C/T allele in the patient and control groups had a significant association with the risk of OLP. In addition, our data revealed that IL-8 + 781 C/T polymorphisms might be associated with the severity of OLP in the Iranian population.

The influence of LPL S447X variants and obesity on lipid profile, oxidative stress, and the risk of T2DM: A case-control study.

Aims: The present study aimed to investigate the association between lipoprotein lipase (LPL) S447X polymorphism and type 2 diabetes mellitus (T2DM), obesity, lipid profile, and oxidative stress parameters in a population from the Kurdistan region of Iraq. Method: We studied 250 adults (51% female and 49% male) aged 45-65 years in four groups, obese and normal body mass index (BMI) diabetic patients versus healthy normal BMI and obese individuals as controls. Lipid profile and oxidative stress parameters were analyzed by colorimetric assay. The LPL S447X genotypes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Results: We found that the obese diabetic group had higher levels of triglycerides (TG), cholesterol, and low-density lipoprotein-cholesterol, and lower level of high-density lipoprotein-cholesterol than other groups. Obese diabetic patients had higher anthropometric indices than nonobese diabetic patients, obese and normal BMI controls. The levels of TG and total oxidative status (TOS) were significantly lower and higher, respectively, in normal BMI controls than in obese controls. Obese diabetic patients had a lower level of total antioxidant capacity than nondiabetic obese controls. The level of TOS was lower in nondiabetic controls compared to the patient groups. Obese diabetic patients had the highest TOS and malondialdehyde levels. The LPL SX genotype was associated with decreased the risk of T2DM by 79% (odds ratio [OR] = 0.21; 95% confidence interval [CI]: 0.05-0.81, p = 0.03). Also, the presence of this genotype reduced the risk of obesity by 39% (OR = 0.61; 95% CI: 0.07-4.90, p = 0.6). In all individuals, the presence of the SX genotype was associated with significantly lower levels of fasting blood sugar (FBS) and TOS. Conclusion: We report the influence of obesity on lipid profile in diabetic and nondiabetic individuals and the effect of LPL SX genotype on decreased risk of T2DM and reduced levels of FBS and TOS.

Association between serum liver enzymes and hypertension using propensity score matching analysis: evidence from a large kurdish prospective cohort study.

BACKGROUND: The association between liver enzymes and hypertension (HTN) has been reported in some studies and the findings are inconsistent. This study was conducted to evaluate the association of liver enzymes with HTN among the Iranian Kurdish population. METHODS: This prospective cohort study was a part of the 5-years (2017-2021) follow-up phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study in Kermanshah province, western Iran.The association between alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glut amyl transferase (GGT), and alkaline phosphatase (ALP) and HTN was investigated by Cox proportional-hazard model (CPHM). We used one-to-one Propensity score matching (PSM) analysis to minimize the effects of confounding factors on the relationship between liver enzymes and HTN . RESULTS: The full population included a total of 8267 participants. According to PSM, for liver enzyme GGT a total of 3664 participants were analyzed. The results of multivariate CPHM showed there is a relationship between participants with high level of GGT and had a higher risk of HTN (HR 1.34; 95% CI: 1.11-1.63). After PSM analysis, the effect of GGT on HTN remained positive and significant (HR 1.48; 95% CI: 1.22-1.78). The 5-years incidence rate of HTN in men and women were 1.27 and 0.81 (person-year), respectively.GGT had the greatest accuracy, which demonstrated an AUROC of 0.7837. CONCLUSION: Results of this study showed GGT could be a potential biomarker among liver enzymes for early detection of HTN. Therefore, monitoring GGT levels is helpful in the early detection of HTN.

New inflammatory biomarkers (lymphocyte and monocyte percentage to high-density lipoprotein cholesterol ratio and lymphocyte to monocyte percentage ratio) and their association with some cardiometabolic diseases : Results from a large Kurdish cohort study in Iran.

BACKGROUND: The incidence of metabolic heart diseases has increased significantly in Middle Eastern countries such as Iran. The present study aimed to investigate the association between monocyte percentage to high-density cholesterol ratio (MHR), lymphocyte percentage to high-density cholesterol ratio (LHR), and lymphocyte to monocyte percentage ratio (LMR) and cardiometabolic diseases in a Kurdish population in the west of Iran. METHODS: This study recruited 9803 individuals, 4728 (48.2%) were male and 5084 (51.8%) were female from Ravansar, Iran. All biomarkers were analyzed by the standard methods. RESULTS: The prevalence of cardiometabolic diseases was higher in overweight/obese participants and increased with age. MHR and LHR increased significantly in cardiometabolic individuals compared with healthy controls. Individuals in the fourth quartiles of LHR and MHR had higher odds ratio (ORs) for metabolic syndrome (MetS) and diabetes mellitus (DM) than the first quartiles. The LMR had a statistical association with non-alcoholic fatty liver disease (NAFLD) ORs and FLI. Besides, all these associations were stronger for females, and increased physical activity decreased inflammatory biomarkers. CONCLUSION: The present study showed MHR and LHR had significant associations with ORs of MetS and DM. Also, MHR and LHR had a significant positive correlation with cardiometabolic risk factors. The LMR only had a statistical association with NAFLD and fatty liver index (FLI). Besides, the strong correlation between inflammatory biomarkers and cardiometabolic risk factors in females might be relevant to higher fat accumulation and metabolic inflammation background, and lower physical activity.

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Association between RBC Indices, Anemia, and Obesity-Related Diseases Affected by Body Mass Index in Iranian Kurdish Population: Results from a Cohort Study in Western Iran.

OBJECTIVE: The relationship between RBC indices and metabolic diseases remains unclear. The association between anemia and obesity is also controversial. The present study aimed to investigate the relationship between RBC indices and metabolic diseases caused by obesity and evaluate the effect of body mass index (BMI) on RBC indices on the Ravansar cohort data. METHOD: For the purpose of this study, 9826 participants aged 35-65 years (5158 females and 4668 males) were recruited in the analyses. A quadratic prediction fit plot investigated the association between RBC indices with BMI and lipid profile. The odds ratio of obesity-related diseases in each quartile category of RBC indices and anemia was estimated using multivariable logistic regression models. RESULTS: Subjects in the fourth quartiles of RBC count, hematocrit (HCT), hemoglobin (HGB), and red cell distribution width (RDW) had a higher risk for obesity-related diseases compared to the first quartiles. However, individuals with the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in fourth quartiles had lower ORs of obesity-related diseases. While BMI reduced the effect of RBC count, HCT, HGB, and RDW on the incidence risk of obesity-related disease, it increased the impact of MCV, MCH, and MCHC. There was a negative association between BMI and RBC indices except for RDW. The BMI effect on RBC indices was different in normal and obese individuals. BMI in mild anemia lowered the risk of metabolic diseases, but it increased the risk of metabolic diseases for moderate anemia. CONCLUSION: A higher risk of obesity-related diseases was observed in the fourth quartiles of RBC count, HCT, HGB, and RDW compared to the first quartiles. However, the incidence risk was lower for MCV, MCH, and MCHC. BMI plays an anemia-type dependent role in the relationship. Consideration should be given to the type of anemia in the relationship between BMI and anemia.

Liver Enzymes and Their Association with Some Cardiometabolic Diseases: Evidence from a Large Kurdish Cohort.

OBJECTIVE: According to reports, liver enzymes might play a role in the incidence and development of cardiometabolic diseases such as metabolic syndrome (MetS), hypertension (HTN), and cardiovascular diseases (CVD). We conducted a study to investigate this hypothesis among the Iranian Kurdish population. METHODS: We analyzed data from the baseline phase of the Ravansar noncommunicable disease (RaNCD) cohort. The association between liver enzymes (ALT, AST, ALT/AST ratio, GGT, and ALP) with cardiometabolic disease risk factors was investigated by multiple linear regression. The odds ratio of cardiometabolic diseases in each quartile category of liver enzyme concentration was estimated using multivariable logistic regression. RESULTS: The mean age of participants was 47.3 ± 4.1 years (48.1 years in males and 51.8 years in females). In the adjusted model, all enzymes were positively associated with MetS, HTN, and CVD risk factors except for the ALT/AST ratio with SBP and DBP. In the adjusted model, subjects in the fourth quartile for GGT, ALT/AST ratio, ALT, ALP, and AST had 3.29-, 2.94-, 2.45-, 2.00-, and 1.19-fold increased risk for MetS compared with subjects in the first quartile. Increased levels of GGT and ALP were positively associated with the risk of HTN (ORs = 1.33, 95%CI = 1.03-1.71 for GGT; ORs = 1.32, 95%CI = -1.68 for ALP). An increased GGT level was significantly associated with CVD (ORs = 1.54, 95%CI = 1.03-1.68). Within the normal range quartile, ALT had a significant correlation with the incidence of MetS. CONCLUSION: According to the present study, the levels of liver enzymes could be considered for early diagnosis of MetS, HTN, and CVD.

Serum level of Xanthine oxidase, Uric Acid, and NADPH oxidase1 in Stage I of Multiple Myeloma.

OBJECTIVE: The etiology of multiple myeloma (MM) is not known. Enzymes such as xanthine oxidase (XO) and NADPH oxidase 1 (NOX1) as relevant sources of reactive oxygen species (ROS) production may play a crucial role in the incidence and progress of MM. Uric acid generated by XO has a controversial dual role in both the prevention and promotion of cancer. We conducted a case-control study and selected patients with stage I MM to investigate the status of XO, NOX1, and uric acid in the patients and controls. METHODS: We used a sample of 33 patients with stage I MM and 30 healthy controls. The enzyme-linked immunosorbent assay (ELISA) measured the enzyme concentration of XO and NOX1, and the colorimetric method measured the serum level of uric acid. RESULTS: Mean serum levels for XO in patients and controls were 6.17±0.83 ng/ml and 4.12±0.57 ng/ml (P<0.001). serum levels of NOX1 were 4.35±1.03 ng/ml in patients and 3.54±0.91 ng/ml in controls (P<0.001). Evaluating the levels of XO and NOX1 in male and female populations showed a significant difference in the male population (NOX1 P=0.002; XO P<0.001) and female population (NOX1 P=0.002; XO P<0.001). Also, a significant correlation was observed between the two enzymes only in the female population (Pearson correlation=0.5; P=0.006). A significant inverse correlation found between albumin and XO (Pearson correlation=-0.7, P<0.001) and NOX1 (Pearson correlation=-0.5, P<0.001). XO was correlated with B2-m (Pearson correlation=0.37, P=0.003). There was no significant difference in uric acid between patients (6.2±1.2 mg/dl) and controls (5.7±1 mg/dl) (P=0.2), and no correlation was found with XO. CONCLUSION: The present study indicates the possible role of XO and NOX 1 in the etiology of MM. Although we found no correlation between uric acid and XO, further studies will help clarify the function of uric acid in the pathogenesis of MM.
.

Serum Levels of Interleukin-8 and Soluble Interleukin-6 Receptor in Patients with Stage-I Multiple Myeloma: A Case-Control Study.

OBJECTIVE: Multiple myeloma (MM) remains an incurable disease that needs better recognition and further research. Previous studies elucidated the interaction between myeloma cells and showed the necessity of bone marrow stromal cells for the initiation and progression of MM. Many chemokines and their receptors including interleukin-8 (IL-8) and soluble interleukin-6 receptor (sIL-6R) play important roles in this interaction. The main purpose of this study is evaluating the serum level of IL-8 and sIL-6R on stage-I of MM patients and healthy controls. METHODS: Serum samples from 30 stage-I MM  patients (13 males and 17 females) and 30 healthy subjects as controls (13 males and 17 females) were examined in this study. The protein concentrations of serum IL-8 and sIL-6R were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean level of IL-8 and sIL-6R were significantly elevated in stage-I MM. The mean levels of IL-8 were 1246.57±279.22 ng/ml in stage-I MM and 902.53± 294.61 ng/ml in controls (P<0.001). The mean levels of sIL-6R were 5.39±1.38 ng/ml and 4.1±1.14 ng/ml in stage-I MM and controls, respectively (P<0.001). The mean levels of IL-8 were 1342.18±193.4 ng/ml in patient females and 859± 278.2ng/ml in control females (P <0.001). The mean levels of sIL-6R were 5.21±1.55 ng/ml and 3.91±1.22 ng/ml in patient females and control females, respectively (P=0.01). The mean level of sIL-6R in patient males and control males were 5.63±1.43 ng/ml and 4.34±1.04 ng/ml, respectively (P=0.01). A significant correlation (Pearson's correlation = 0.45, P=0.008) was observed in the population of females (patients and controls). CONCLUSION: The results of study suggest the possible involvement of IL-8 and the sIL-6R at stage-I MM and can better characterize the role of chemokines and their receptors in the disease process, especially in the early stages.