Berrin Karadağ

Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer's disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder with a poorly understood etiology. There is considerable evidence that oxidative stress occurs in AD and increased DNA damage has been found in brain tissues and leukocytes of AD patients. Base excision repair (BER) is the major pathway responsible for removing oxidative DNA damage. Polymorphisms in DNA-repair genes have been associated with the increased risk of several age-related disorders including various types of cancer and could also be related to the etiology of AD. We conducted a case-control study including 91 patients with AD and age- and sex-matched 93 control subjects to examine the role of single nucleotide polymorphisms of BER genes, hOGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC1 (Arg280His and Arg399Gln) as a risk factor for AD. The frequencies of the hOGG1-Ser326Cys, APE1-Asp148Glu and XRCC1-Arg280His and XRCC1-Arg399Gln variant alleles in our control group were 0.23, 0.31, 0.10 and 0.33, respectively. No significant association was observed between the variant alleles of hOGG1-Ser326Cys (OR=1.32, 95% CI=0.83-2.11), APE1-Asp148Glu (OR=1.08, 95% CI=0.70-1.68), XRCC1-Arg280His (OR=0.53, 95% CI=0.24-1.14) and XRCC1-Arg399Gln (OR=1.05, 95% CI=0.68-1.63) and AD. Our results suggest that the polymorphic variants of these BER genes are not independent risk factors for AD.

The combinations of TNFα -308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease.

Objective –  Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor α (TNFα), interleukin (IL)‐6 and IL‐10 have been suggested to influence the risk of Alzheimer’s disease (AD) with conflicting results.

Comparison of epicardial adipose tissue (EAT) thickness and anthropometric measurements in metabolic syndrome (MS) cases above and under the age of 65

EAT is a new index of cardiac and visceral obesity. Waist circumference (WC) measurement is not fully reliable in the determination of visceral adipose tissue (VAT), especially in elderly individuals. Studies on the reflection of the intra-abdominal fat mass by the EAT mass surrounding the heart were performed. Our purpose in this study was to determine the relation between the MS criteria and EAT in MS cases and especially to compare anthropometric measures between non-geriatric patients under the age of 65, and geriatric ones over the age of 65 years. The study was performed during the years 2008 and 2009 on 120 cases; 66.7% of them were under the age of 65 and 33.3% of the cases were 65-year old or older. All of the patients were diagnosed as MS by the International Diabetes Federation (IDF) criteria. They were randomized as per the application order and included to the study. Each subject underwent transthoracic two-dimensional (2D) guided M-mode echocardiogram. We measured epicardial fat thickness on the 1/3 section close to the ventricle basis adjacent to the free wall of right ventricle from both the parasternal long axis (LA) and parasternal short axis (SA) views. Multiple regression analysis showed that WC, systolic blood pressure (SBP) and age were the strongest independent variables correlated with EAT (p<0.001). We also determined a significant correlation between low-density lipoprotein-cholesterol (LDL-C) and EAT (p<0.05). Our data show that EAT-measurement by echocardiography is an efficient method in determination of visceral adiposity and shall be taken into consideration especially when advanced age groups are in question.

Polymorphisms in the DNA repair genes XPD (ERCC2) and XPF (ERCC4) are not associated with sporadic late-onset Alzheimer's disease.

Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing a variety of helix-distorting lesions. Xeroderma pigmentosum group D (XPD) and group F (XPF) are essential participants in NER pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A; exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA repair activities. Alzheimers disease (AD) is characterized by progressive neuronal loss correlated in time with the symptoms of disease considered. Although deficient DNA repair was proposed in the etiology of AD by several researchers, polymorphisms of DNA repair genes have not been studied in AD yet. We conducted a case-control study including 97 patients with AD and age- and sex-matched 101 control subjects to examine the role of genetic polymorphisms of XPD and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group were 0.41, 0.35, and 0.35, respectively. No significant association was observed between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon 23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and AD. Our results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD.

The combination of ınterleukin-10 − 1082 and tumor necrosis factor α − 308 or ınterleukin-6 − 174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis

BACKGROUND The etiopathogenesis of Hashimotos thyroiditis (HT) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with HT, and to evaluate the relationship between genotypes and clinical/laboratory manifestation of HT. METHODS Tumor necrosis factor α (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 G-1082A (rs 1800896) single nucleotide polymorphisms (SNPs) in DNA from peripheral blood leukocytes of 190 patients with HT and 231 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. RESULTS There was no notable risk for HT afflicted by TNFα -308, IL-6 -174 and IL-10 -1082 polymorphisms alone. However, carriers of variant alleles of both IL-10 -1082 and TNFα -308 polymorphisms had four-fold times higher risk for HT in comparison with non-carriers. Additionally, concomitant presence of both mutant IL-10 -1082 A and IL-6 -174 C alleles raised three-fold the HT risk. CONCLUSION Our results suggest that the combined effects of TNFα -308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for HT.

Use of knee height for the estimation of stature in elderly Turkish people and their relationship with cardiometabolic risk factors

The determination of the approximately truest value in height measurement is important in many fields, but it is difficult to perform true measurements, especially in the elderly individuals. We planned to investigate the following items in geriatric Turkish population: to calculate the decrease in height with advancing age by using the standing height measurement and estimated height derived from the knee height; to evaluate the significance of difference between the two measurement methods in the calculation of body mass index (BMI) and waist/height ratio (WHtR); to determine the cut-off value of WHtR according to estimated height in elderly individuals. We studied 551 cases aged between 19 and 97 years. Knee height was measured using a sliding caliper in a sitting position. Linear regression analysis was carried out to derive predictive equations for the estimation of stature with adults (≤ 50 years of age) according to the gender. This equation was then used to estimate height among elderly subjects. Of the cases, 60.3% were <60 years (mean: 48.75 ± 7.50); 39.7% of the cases were >60 years (mean: 69.51 ± 7.12). Estimated BMI (EBMI) measurements in the females and males >60 years were in average 1.23 kg/m(2) and 0.92 kg/m(2) higher than their real BMIs, respectively. EBMI measurements in the females <60 years were 0.32 kg/m(2) higher than their real BMIs (p<0.01). There is a statistically significant difference between WHtR in the females of both age groups, and in the males >60 years, as compared to our estimated WHtR (EWHtR) measurements (p<0.01). The cut-off point of WHtR was 0.61 and 0.58 in the female and male cases of >60 years in our study, respectively. WHtR seemed to be a better anthropometric index that could predict most cardiometabolic risk factors in our study. EWHtR emerged to be a better cardiometabolic risk index especially in the elderly group.

An unusual case of biliary obstruction caused by Dicrocoelium dentriticum.

Dicrocoelium dentriticum (D. dentriticum) is a liver fluke induced biliary obstruction. Infection usually occurs in herbivores such as sheep, goats and deer; human infection is very rarely encountered in clinical practice. We report on a 65-y-old female presenting with biliary obstruction caused by D. dentriticum. Following treatment with triclobendazole, her symptoms disappeared, and laboratory values returned to normal range within 6 months. Parasitosis is an important cause of biliary obstruction. We suggest that for patients presenting with biliary obstruction, D. dentriticum should be included in the differential diagnosis.

Relationship between left atrial volume index and cognitive decline in elderly patients with sinus rhythm

Left atrial (LA) enlargement is a predictor of cardiovascular outcomes such as atrial fibrillation (AF), stroke, and death. The aim of this study was to explore the relationship between LA size and cognitive function in elderly patients without any signs of clinical dementia, AF or previous stroke. We assessed the cognitive status and LA volume (LAV) of 108 consecutive patients (27 males; mean age, 74.8 ± 6.9 years) with sinus rhythm. Cognitive status was assessed by the Mini Mental State Examination (MMSE). Patients with a MMSE score of ≤25 were considered to have cognitive impairment. LAV was measured with two-dimensional echocardiography. LAV index (LAVI) was obtained by indexing LAV to body surface area. Thirty-five patients (32.4%) had cognitive impairment. The patients with cognitive impairment had significantly larger left atria than the patients with normal cognitive function. Receiver operating characteristic analysis revealed a cut-off point of ≥ 34 mL/m(2) for LAVI to predict patients with cognitive impairment (sensitivity, 97.1%; specificity, 52.1%; positive predictive value, 49.3%; negative predictive value, 97.4%). LAVI ≥34 mL/m(2) was significantly associated with cognitive impairment (p = 0.001, odds ratio = 36.91, 95% confidence interval = 4.8-284.2). Logistic regression analysis revealed that LAVI ≥ 34 mL/m(2) and age were independently associated with cognitive impairment. Increased LAVI is associated with cognitive impairment. Assessment of cognitive function may be recommended in elderly patients with enlarged left atria.

Lack of association between intercellular adhesion molecule-1 (ICAM-1) polymorphisms and polycystic ovary syndrome

PurposeThis study examined the possible association of G241R and K469E single nucleotide polymorphisms (SNPs) of ICAM-1 gene with the occurrence and clinical/biochemical characteristics of polycystic ovary syndrome (PCOS).MethodsG241R and K469E SNPs in DNA from peripheral blood leukocytes of 169 PCOS and 259 healthy control women were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes.ResultsWe did not find significant differences in the distributions of G241R and K469E polymorphisms, nor in the haplotype frequencies between PCOS and control women. None of the studied polymorphisms were found to affect insulin resistance indices significantly.ConclusionsThese preliminary results suggest that the 241 and 469 SNPs of ICAM-1 gene may not be risk factors for PCOS. Further studies with a larger cohort, analyzing other ICAM-1 polymorphisms are necessary to support our observations before any statement can be made about the relationship between PCOS and ICAM-1 polymorphisms.

Replicability and reliability of pain assessment forms in geriatrics

Aim of the study was to investigate the replicability and reliability of the multi-dimensional health assessment questionnaire (MDHAQ) and visual analog scale (VAS) in young and elderly individuals with chronic pain. Ambulatory patients, 20 of them aged above 65 years and complaining about chronic pain and 20 patients with the age of 40 and younger working in a factory were assessed with VAS and MDHAQ. The assessment was repeated to investigate the replicability and reliability of both tests. According to MDHAQ disability index (DI), the elderly had more complains on the first and second day of the study (p<0.001). In terms of changes between first and second days, DI scores of the elderly group (r=0.634; p=0.003) and the younger group (r=0.888; p<0.001) had quite similar responses. Criteria for the assessment of pain, fatigue and general condition according to MDHAQ were similar in both groups in terms of changes between first and second day of the study, there was no significant differences between the groups. But while responses in the younger group according to these 3 parameters were highly reliable, the elderly groups responses were reliable only for their last week pain assessment. Both tests were replicable in the elderly group, VAS and MDHAQ were especially applicable for the last time phase of their pain; while fatigue, general health condition and DI indicated diminished reliability in the elderly group, compared to the young group.