Investigation of relationship between IL-6 gene variants and hypertension in Turkish population

Hypertension (HT) is a common and life threating health problem worldwide leading to stroke, heart attack and renal failure. It is characterized by elevated blood pressure forced heart load. Human interleukin-6 (IL-6) and C- reactive protein (CRP) are known to be involved in inflammatory processes. IL-6 gene is a polymorphic gene which −174 G/C is a common and −572 G/C is a rare polymorphisms identified in promoter region. Publications on IL-6 gene polymorphisms raised the question whether this gene polymorphisms lead to susceptibility to HT or not. To investigate the effects of IL-6 gene −174 G/C (rs 1800795) and −572 G/C (rs1800796) polymorphisms on plasma IL-6 and CRP levels and their associations with hypertension disease in Turkish population we analyzed −174 G/C and −572 G/C polymorphisms and plasma IL-6 and CRP levels in 111 healthy controls and 108 hypertension patients from Adıyaman, Turkey. We determined the genotypes using polymerase chain reaction-restriction fragment length polymorphism and analyzed plasma levels of IL-6 by ELISA and CRP by automated standard biochemical methods. We have found no statistically significant differences between IL-6 gene −174 G/C and −572 G/C genotypes and allelic frequencies and IL-6 and CRP plasma levels and HT (p > 0.05). No CC genotype was found in control subjects for −572 G/C polymorphism. In conclusion, we found relation to −174 G/C and −572 G/C gene variants between neither IL-6 and CRP levels nor hypertension. The −572 G allele and GG genotype are predominant in Turkish population in Adıyaman, Turkey whereas the CC genotype is very rare.     

Relationship between root caries and cardiac dysrhythmia

doi: 10.1111/j.1741‐2358.2010.00367.x
Relationship between root caries and cardiac dysrythmia Background: Cardiac dysrhythmia are frequently found in the elderly population because of conduction system disease and ageing. Recent reports have suggested that dental caries and periodontal disease are predictors of coronary heart events. However, this hypothesis remains largely unproven. Objective: This study investigated the relationship between root caries and cardiac dysrhythmia in an elderly population. Subjects and methods: Among 600 subjects, 233 who were dentate at baseline underwent a baseline examination and subsequent annual investigations, including an oral examination and a 12‐lead electrocardiogram, for a 4‐year period. Analysis of covariance (ancova) was used to assess the number of sites with root caries between subjects with mean C‐reactive protein (CRP) serum level of <3.0 mg/l and those with the mean CRP serum level ≥3.0 mg/l. Logistic regression analysis was performed to assess relationship between root caries and cardiac dysrhythmia. Results: A high mean CRP serum level group had a significantly higher number of sites with root caries than a low CRP group (p < 0.001). Number of sites with root caries events was significantly associated with cardiac dysrhythmia among non‐smokers (odds ratio, 5.84; p = 0.040). These results suggest that root caries is related to the incidence of dysrhythmias in non‐smokers. Conclusions: We conclude that non‐smoking elders with root caries lesions are at an elevated risk for dysrhythmias.     

Association of Cholecystokinin 1 Receptor and β3‐Adrenergic Receptor Polymorphisms with Midlife Weight Gain

We investigated the relationship of polymorphisms in the cholecystokinin 1 receptor [CCK1R; G to T (n‐128), A to G (n‐81)] and the β₃‐adrenergic receptor (β₃‐AR; Trp64Arg) with midlife weight gain. The participants were 1012 Japanese men and women (40 to 59 years of age). Their weight at 18 years old was obtained from a questionnaire. Weight change was defined as the current weight minus the weight at 18 years old. Subjects were grouped into four categories by these genotypes: W/W = noncarriers, W/H = Arg⁶⁴ carriers of the β₃‐AR, H/W = T (n‐128) or G (n‐81) carriers of the CCK1R, H/H = T (n‐128) or G (n‐81) and Arg⁶⁴ carriers. In men, the interaction between the CCK1R and β₃‐AR polymorphisms was significant (two‐way ANOVA, p < 0.05), but neither the CCK1R nor the β₃‐AR was individually associated with weight gain. The H/H group showed a higher possibility of weight gain of 10 kg or more compared with the W/W group in men. The odds ratio for weight gain (≥10 kg) of H/H was 2.54 (95% confidence interval: 1.50 to 4.30) compared with W/W. In women, neither main effect nor interaction was significant. These results suggest that the combination of CCK1R and the β₃‐AR polymorphisms is a contributing factor for midlife weight gain in men.     

Productivity enhancement of recombinant protein in CHO cells via specific promoter activation by oncogenes

To construct a recombinant protein highly producing cell lines, we have previously developed the Oncogene Activated Production (OAP) system by using BHK-21 cells. Here we verified the availability of the OAP system in CHO cells. We firstly generated ‘primed’ ras amplified CHO cells, ras clone I, by introducing human c-Ha-ras oncogene into CHO cells. This ras clone I enables quick and easy establishment of recombinant protein hyper producing cell lines by introduction reporter gene of interest. Then we generated I13 by introducing human interleukin 6 (hIL-6) gene as a reporter gene, which showed enhanced productivity rate as compared to A7 established by conventional method. Furthermore, we found that hIL-6 production level of I13 was slightly improved by raising the CO₂ concentration from 5 to 8% possibly because of the enhanced growth rate. We further introduced the E1A oncogene, which has been shown to have a synergistic effect on the recombinant protein production of the ras-amplified BHK-21 cells, then evaluated the productivity. When culture in 5% CO₂ condition, only the slight effect can be seen. However when cultured in 8% CO₂ condition, not only cell number, but also productivity increased significantly, resulted in great augmentation of hIL-6 production, maximum production being 88.6 μg/ml/3 days. This study demonstrates that recombinant protein production level reached commercially desirable level by utilizing our OAP system in CHO cells and optimizing the culture condition. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effects of the binding of calcium ions on the structure and dynamics of the ΦX174 virus investigated using molecular dynamics

It is known that the presence of calcium ions (Ca^2 +) is necessary for the enterobacterial virus ΦX174 to inject its DNA into the host cell, and that some mutations in the major capsid proteins lead to better survivability at higher temperatures. Our goal in the current study is to determine the physical changes in both the wild-type and mutant virus due to the binding of Ca^2 +. Thus, we performed molecular dynamics simulations of the ΦX174 major capsid protein complex with and without Ca^2 + bound. Our results show that binding of Ca^2 + leads to energetic and dynamical changes in the virus proteins. In particular, the results suggest that binding of Ca^2 + is energetically favorable and that the mutation leads to increased fluctuations of the protein complex (especially with the calcium ions bound to the complex), which may increase the rate of genome packaging and ejection for ΦX174.