Association of MIF-173G/C, IL-4 VNTR, and IL-1RA VNTR variants with FMF-related amyloidosis in a Turkish cohort.

The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis. The aim of this study is to investigate the risk of developing FMF-related amyloidosis with macrophage migration inhibitory factor (MIF), interleukin 4 (IL-4), and IL-1 receptor antagonist (IL-1RA) variants. This study included 62 FMF patients with amyloidosis, 110 FMF patients without amyloidosis, and 120 controls. The clinical information of the patient groups was compared. MIF-173G/C, IL-4 variant number tandem repeat (VNTR), and IL-1RA VNTR variants were analyzed for all participants. The use of colchicine, pleurisy, and appendectomy was more common in FMF patients with amyloidosis than in FMF patients without amyloidosis. MIF-173G/C C/C genotype and C allele were higher in both patient groups compared to controls. IL-1RA VNTR A1/A2 and A1/A4 genotypes and A1-A4 alleles were more common in both patient groups than controls. The IL-4 VNTR P1 allele was more common in FMF patients with amyloidosis compared to controls. The MIF-173G/C allele and the IL-1RA VNTR A1-A4 allele are associated with FMF in the Turkish population but not with amyloidosis risk in FMF patients. The IL-4 VNTR P1 allele is more common in FMF patients with amyloidosis than in healthy individuals.

Cardiologists' Awareness of the Relationship Between Periodontal Diseases and Cardiovascular Diseases: A Region-Wide Survey in Türkiye.

OBJECTIVE: The relationship between oral health and general health has gained increased attention in recent years. This study sought to assess the knowledge, attitudes, and practices of cardiologists in Türkiye concerning the link between periodontal disease and cardiovascular disease (CVD). METHODS: After a pilot test, a modified survey was dispatched to 1,894 practicing cardiologists in Türkiye. Two mailings were carried out, and descriptive statistics were used to analyze the data. RESULTS: Of the 1,894 cardiologists surveyed, 166 responded, yielding a response rate of 11.5%. The majority of respondents (77%) were male and held professional positions in academia (45%), as assistant doctors (17.5%), or in private practice (12.7%). Ninety percent of respondents accurately recognized periodontal disease as a chronic, multifactorial inflammatory disease. Meanwhile, 78% concurred that inflammation is a pivotal connection between periodontal disease and CVD. On the topic of whether treating periodontal disease could reduce a patient's CVD risk, 37% of the polled cardiologists expressed uncertainty, while 9% disagreed. Seventy six percent believed that periodontists and cardiologists should collaborate to reduce shared risk factors for both cardiovascular and periodontal diseases. Additionally, 80% expressed interest in deepening their understanding of the link between periodontitis and CVD. CONCLUSION: While the vast majority of participants acknowledged that microbially-associated, host-mediated inflammation is a hallmark of periodontitis, consensus was lacking on inflammation being the primary factor linking periodontal diseases and CVDs. The majority of respondents expressed eagerness understand better the relationship between these two diseases, with the intention of enhancing oral health content in medical school and attending relevant seminars.

[Mortality prediction ability of phycians in intensive care units of Turkey (MOPAP)]. / Türkiye'de yogun bakim ünitelerinde hekimin mortaliteyi öngörebilme gücü.

INTRODUCTION: Intensive care physicians are increasingly involved in decision making about the prognosis of intensive care unit ICU patients. With this study; we aimed to evaluate the power of clinician foresight at prediction of mortality in patient at triage to intensive care and patient follow-up. MATERIALS AND METHODS: This study was conducted in ICUs located in various geographical regions of Turkey between January 1, 2017-April 30, 2017.The clinical research was planned as observational, multicenter, cross-sectional. RESULT: A total of 1169 intubated patients were followed in 37 different ICU. At the beginning of the follow-up we asked the physician who will follow the patient in the ICU to give a score for the probability of survival of the patients. Scoring included a total of 6 scores from 0 to 5, with the "0" the worst probability "5" being the best. According to this distribution, only 1 (0.9%) of 113 patients who were given 0 points survived. Three (6.1%) of 49 with the best score of 5 died. Survival rates were significantly different in each score group (r: -0.488; p<0.001). After the combined mortality estimation scores based on the clinical observations of the physicians (0 and 1 point score was combined as non-survive, 4 and 5 score was combined as survived) 320 of the 545 patients were estimated to be dead and 225 were predicted survival. Sensitivity and spesifity of scoring system to predict mortality was 91.56% (95% CI: 87.96-94.37), 76.89% (95% CI: 70.82-82.23) respectively. CONCLUSIONS: In this study, we concluded that the physicians who follow the patients in the ICU can predict the poor prognosis at the time of admission and the high mortality rate. The physician's opinion on mortality estimation should be considered in intensive care mortality scoring in addition to other laboratory and clinical parameters.

Prevalence of insulin resistance and identifying HOMA1-IR and HOMA2-IR indexes in the Middle Black Sea region of Turkey.

BACKGROUND: Insulin resistance (IR) is one of the most important etiological risk factors in the development of diabetes. However, there is no clear data regarding the prevalence of IR in the country. OBJECTIVE: This study evaluates the prevalence of IR and identifies the optimal threshold values for the HOMA indexes in Turkey. METHODS: This cross-sectional, population-based survey includes 2013 participants aged 20-84 years. The values of the anthropometric measurements and laboratory analysis were recorded. The 90th percentile in the non-obese and non-diabetic population was accepted as cut-off values for IR. RESULTS: The optimal threshold values for IR were 2.46 in HOMA1-IR and 1.40 in HOMA2-IR. Using the HOMA2-IR method, the overall prevalence of IR was 33.2%. The IR prevalence was higher in women (35.6%) compared to men (30.1%) [p=0.008]. There was a higher IR prevalence in men living in urban areas (p=0.001), not in women. The multivariate logistic regression analysis showed that gender, serum glucose level, serum levels of triglycerides and high-density lipoprotein cholesterol, bodymass index and income status were associated with insulin resistance. CONCLUSION: The cut-off values of HOMA1-IR and HOMA2-IR were determined in this study and we believe that these findings will be helpful to clinicians in the fight against health problems such as diabetes.

Angiotensin Converting Enzyme Gene Insertion/Deletion Variant and Familial Mediterranean Fever-related Amyloidosis.

INTRODUCTION: The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis, which can lead to kidney failure. Genetic variability in the genes of various components of the renin-angiotensin system may play a role in the pathogenesis of the kidney disorders.  The aim of the present study was to investigate the association between angiotensin converting enzyme (ACE) gene I/D variant and risk of developing FMF-related amyloidosis in Turkish patients. MATERIALS AND METHODS: A total of 240 individuals consisting of 40 patients with FMF-related amyloidosis, 100 FMF patients without amyloidosis, and 100 healthy controls were recruited. For all of the participants, ACE I/D variant was detected by the polymerase chain reaction using specific primers. RESULTS: A significant difference was found between the patients with FMF-related amyloidosis and the control group as for genotype distribution of ACE I/D variant (P < .05). The ACE D/D and I/D genotypes were more frequent in the patients with FMF-related amyloidosis while the I/I genotype was less frequent in the same patients. The FMF patients (with and without amyloidosis) had significantly higher percentages of the D/D and I/D genotypes than the healthy controls (P < .05). Comparison between the subgroups of FMF patients, divided into those with and without amyloidosis, yielded a significant correlation according to ID+II versus DD genotypes (P < .03, odds ratio, 3.24; 95% confidence interval, 1.05 to 12.01).  Conclusions. Based on these observations, the ACE I/D variant D/D genotypes implicate a possible risk in the FMF-related amyloidosis among Turkish population.

Association between Vitamin K Epoxide Reductase (VKORC1) -1639G>A Polymorphism and Osteoporosis in Postmenopausal Women.

Introduction: Osteoporosis is a common disease, and several factors contribute to its development. Recently, there has been increasing evidence that vitamin K (VK) plays a critical role in maintaining bone strength. Vitamin K serves as a co-factor for the γ-carboxylation of particular proteins to convert specific glutamic acid residues to γ-carboxyglutamic acid residues. This process involves two enzymes, γ-glutamyl carboxylase and vitamin K epoxide reductase (VKORC1). The number of studies investigating the effects of VKORC1 gene mutations on bone mineral density in postmenopausal osteoporosis patients is limited. The aim of this study was to investigate the relationship between the VKORC1 -1639G>A polymorphism and osteoporosis in postmenopausal Turkish women. METHODS: The study group consisted of 176 postmenopausal women with osteoporosis and 140 healthy postmenopausal women. The selection criteria for the healthy controls included non-osteoporotic bone mineral density (BMD) and similar demographic characteristics to the osteoporosis group. The genotyping of the VKORC1 -1639G>A polymorphism was conducted using the restriction fragment-length polymorphism method. RESULTS: We found that the genotype frequencies of the GG, GA and AA genotypes were 25.6, 64.2 and 10.2% in the patients and 33.6, 55.8 and 10.7% in the controls, respectively. In the patient and control groups, the genotype distribution of the studied locus was found to be non-compatible with Hardy-Weinberg equilibrium. We found a nonsignificant association between the -1639G>A polymorphism in the VKORC1 gene and osteoporosis in postmenopausal Turkish women. CONCLUSION: We have shown that the VKORC1 -1639G>A polymorphism is not a risk factor for postmenopausal osteoporosis.

MTHFR gene C677T and A1298C variants are associated with FMF risk in a Turkish cohort.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine (Hcy) metabolism. We aimed to evaluate a possible relationship between MTHFR gene C677T (rs 1801133), A1298C (rs 1801131) variants and susceptibility to FMF in a Turkish cohort. MATERIAL-METHODS: This case-control study included 198 Turkish FMF patients and 100 healthy subjects as controls. MTHFR C677T and A1298C were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. RESULTS: The genotype distribution and allele frequency of the MTHFR C677T were statistically different between the patients and the control group (P=.006, P=.001, respectively). The frequency of the TT genotype and T allele of MTHFR C677T was significantly higher in the patients than in the controls. The genotype distribution of MTHFR A1298C variant did not show any statistically significant difference between the patients and the controls (P>.05). The patients had statistically different frequencies in allele C of MTHFR A1298C variant compared with the control (P=.032). We also examined the risk associated with inheriting the combined genotypes for the two MTHFR variants. According to these results, individuals who were CC homozygous at C677T locus and AA homozygous at A1298C locus have a lower risk of developing FMF (P=.002). Individuals who were TT homozygous at C677T locus and AC heterozygous at A1298C locus have higher risk of developing FMF (P=.033). CONCLUSION: Our findings clearly showed there was an association the MTHFR C677T/A1298C variants and susceptibility to FMF in the Turkish sample.

Single nucleotide polymorphism of adiponectin +276 G/T is associated with the susceptibility to essential hypertension in a Turkish population.

BACKGROUND: It is well known that arterial stiffness is associated with hypertension. Recent studies have shown that adiponectin +276 G/T, ACE I/D, AGTR1 A1166C, and eNOS E298D polymorphisms are likely to be risk factors for arterial stiffness. In this study, we aimed to investigate possible associations between these single-nucleotide polymorphisms (SNPs) and essential hypertension in a Turkish population. METHODS: The study population consisted of 170 patients who were diagnosed with essential hypertension and 170 sex- and age-matched controls. Genotyping of adiponectin +276 G/T, ACE I/D, AGTR1 A1166C, and eNOS E298D SNPs were performed using real-time polymerase chain reaction and commercially produced kits. RESULTS: The percentage of the adiponectin +276 T allele carriers was significantly higher in the patients with hypertension (33%) than in the controls (25%, p < 0.011). Through multiple logistic regression analysis, the adiponectin +276 T allele carrier was found to be associated with an increased risk of hypertension (TT vs. GG and TG: odds ratio = 3.318, p = 0.014, 95% confidence interval: 1.269-8.678). The genotype distributions or allelic frequencies of ACE I/D, AGTR1 A1166C, and eNOS E298D SNPs did not significantly differ between the patients with hypertension and the controls. CONCLUSION: The present study demonstrated that the adiponectin +276 G/T SNP is likely to be a risk factor for essential hypertension in a Turkish population.

Mutational Spectrum of the MEFV Gene in AA Amyloidosis Associated With Familial Mediterranean Fever.

INTRODUCTION: Familial Mediterranean fever (FMF) is a recessively inherited disease which is characterized by recurrent episodic fever, abdominal pain, and polyserositis. It is caused by mutations in the MEFV gene, encoding the pyrin protein. The most important complication of FMF is secondary (AA) amyloidosis that leads to kidney failure. This study aimed to identify the frequency and distribution of MEFV mutations in Turkish patients with FMF-associated AA amyloidosis. MATERIALS AND METHODS: A total of 57 patients with FMF-associated AA amyloidosis and 60 healthy controls were included in this study. We analyzed the MEFV gene for E148Q, M694V, M680I, and V726A mutations and R202Q variant by polymerase chain reaction and restriction fragment length polymorphism methods.  Results. The male-female ratio was 0.72. The mean age of the patients was 29.8 ± 12.8 years. Among the patients, the rate of the MEFV mutations was found to be 77.2%. The most frequently observed genotype was homozygous M694V mutation, which was present in 17 patients (29.8%, P < .001), followed by compound heterozygous M680I/M694V (14.3%, P = .01). The R202Q allele frequencies were significantly different between patients and control group (P = .02; odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94). CONCLUSIONS: In this study, mutation analysis of MEFV gene confirmed that the most frequent mutation was homozygous M694V genotype. R202Q may be important in patients with FMF-associated AA amyloidosis. Thus, it is suggested that investigation of R202Q should be considered as a genetic test for Turkish FMF patients.

Interleukin-1Ra rs2234663 and Interleukin-4 rs79071878 Polymorphisms in Familial Mediterranean Fever.

OBJECTIVE: Familial Mediterranean Fever (FMF) is an autosomal recessively inherited auto inflammatory disorder. MEFV gene, causing FMF, encodes pyrin that is associated with the interleukin-1 (IL-1) related inflammation cascade. The aim of this study was to investigate the relationship of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-4 (IL-4) polymorphisms with the risk of FMF in the Turkish population. METHODS: This study included 160 patients with FMF (74 men, 86 women) and 120 healthy controls (50 men, 70 women), respectively. Genotyping of IL-1Ra rs2234663 polymorphism was evaluated by gel electrophoresis after polymerase chain reaction (PCR). The IL-4 rs79071878 polymorphism was determined by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis. The results of analyses were evaluated for statistical significance. RESULTS: There was no significant difference in IL-1Ra genotype and allele distributions between FMF and the control groups (p>0.05). However, a significant association was observed between FMF patients and control groups according to IL-4 genotype distribution (p=0.016), but no association was found in the allelic frequency of IL-4 between FMF patients and the controls (p>0.05, OR: 1.131, CI 95%: 0.71-1.81). CONCLUSIONS: The IL-4 rs79071878 polymorphism, was associated whereas the IL-1Ra rs2234663 polymorphism was not associated with FMF risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of IL-1Ra and IL-4 polymorphism on the risk of developing FMF.

The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis.

Preliminary evidence suggests that a higher neutrophil-lymphocyte ratio (NLR) may be an indicator of active ulcerative colitis (UC). However, it is not clear whether the NLR is a useful and simple indicator of clinical activity in UC after adjusting for the other inflammatory markers. We designed a retrospective study to evaluate the role of the NLR in estimating disease severity in UC patients. The study consisted of 71 patients with UC and 140 age- and sex-matched healthy individuals (control group). The NLR, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count were measured. The NLR values of the active UC group were elevated compared with those of the patients with inactive UC and the controls (2.59 ± 1.47, 2.03 ± 1.07, and 1.98 ± 0.85, respectively; p = 0.005). The receiver operating characteristic revealed that the optimum NLR cut-off point for active UC was 2.39. A multivariable logistic analysis showed that of the parameters studied, C-reactive protein was the only parameter able to significantly discriminate active from inactive UC (B: 0.222; p = 0.017; odds ratio: 1.248; 95% confidence interval: 1.041-1.497).

A rare cause of pericardial effusion: giant cell arteritis.

Giant cell arteritis is a granulomatous vasculitis characterized by medium or large sized vessel involvement. Although extracranial branches of the carotid artery are typically involved, involvement of aorta and its major branches can also be seen. Cardiac involvement has been encountered less frequently and pericardial effusion is rarely encountered. In this paper, a case has been presented in which pericardial effusion was determined during the examination and diagnosis was giant cell arteritis.

High association of IL-4 gene intron 3 VNTR polymorphism with diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a common disease. It is one of the late complications of diabetes mellitus. DPN can lower the quality of life by causing severe painful clinic symptoms. The aim of this study is to evaluate interleukin (IL)-4 gene variable number of tandem repeat (VNTR) polymorphism on DPN in Turkish population. Two hundred and twenty-seven DPN patients and 241 controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction analyses for the IL-4 gene intron 3 VNTR polymorphism. The distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between DPN patients and control group (p = 0.001). The frequency of P1 and P2 alleles was statistically different between DPN patients and control group (p = 0.00009). The results of this study suggested that intron 3 VNTR polymorphism of the IL-4 gene plays an important role in the occurrence of DPN in the Turkish population.

Decreased vitamin D levels in patients with familial mediterranean fever.

Familial mediterranean fever (FMF) is an autosomal recessive disorder caused by mutations in the FMF gene (MEFV). The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. Since there are several etiological factors, FMF is the most common periodic fever syndrome. However, it is still unknown what triggers or ends these periodical attacks. As a pleiotropic hormone, vitamin D has immunomodulation effects. The aim of this study was to evaluate the vitamin D levels in FMF patients. The study group was comprised of 26 patients diagnosed with FMF (men/women: 12/14), and 34 healthy control (men/women: 17/17). Vitamin D levels in FMF patients and healthy controls were 11.05 ± 7.11, 17.15 ± 6.49, respectively. FMF patients had significantly decreased vitamin D levels compared with healthy controls (P < 0.001). In conclusion, it is thought that vitamin D deficiency in FMF patients may trigger the attacks. Further studies with larger patient populations need to hold to investigate the vitamin D deficiency in patients with FMF and that may assist to clarify the mechanism behind the colchicines resistant cases.

The frequency of antibodies against cyclic citrullinated peptides and rheumatoid factor in healthy population: a field study of rheumatoid arthritis from northern Turkey.

Rheumatoid arthritis (RA) is a chronic, systemic and an autoimmune disease characterized by inflammation of the synovial membrane that affects approximately 1 % of the total world population. Rheumatoid factor (RF) is a widely used auto antibody in diagnosis of the RA and found positive in 50-80 % of the patients but with a lower specificity. On the other hand, anti-cyclic citrullinated peptide (anti-CCP) is the latest serological marker with a specificity around 98 %. This field survey was conducted in different regions to investigate the frequency of RF and anti-CCP and also frequency of RA in a northern province of Turkey. This study was conducted in 70 local areas (12 urban and 58 rural) in the province of Tokat, which is located in northern Turkey. The population of Tokat was reported to be 828,000 at the last census and about 530,000 individuals aged > 18 years old. The study population of 941 subjects (462 male and 479 female; urban 501 and rural 440) was selected by random sampling method among 530,000 individuals. Of the 941 healthy controls assigned to the study, 479 of them were female (51 %) and 462 of them were males (49 %), and median age of all participants was 41 ± 17. Twenty-six subjects were RF positive (2.8 %), and 9 patients were anti-CCP positive (1 %). The presence of both RF and anti-CCP antibodies has also been shown in two patients (0.2 %). In conclusion, we demonstrated that the frequency of RA was 0.53 %, RF presence was 2.8 %, and anti-CCP presence was 1 % in total 941 healthy subjects enrolled into study.

Significance of MEFV gene R202Q polymorphism in Turkish familial Mediterranean fever patients.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. The disease is associated with mutations in the Mediterranean fever (MEFV) gene, which encodes for the pyrin protein. The aim of this study was to explore the frequency and clinical significance of the R202Q (c.605G>A) polymorphism in exon 2 of the MEFV gene in a cohort of Turkish patients with FMF. METHODS: The study included 191 patients with FMF and 150 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MEFV gene R202Q polymorphism. RESULTS: The genotype and allele frequencies of R202Q polymorphism showed a statistically significant difference between FMF patients and controls (p<0.0001 and p=0.0004, respectively) and especially the homozygous AA genotype was significantly higher in FMF patients than healthy controls (p=0.0002; odds ratio=6.27; 95% CI=2.1-18.3). However no significant association was observed between clinical and demographic features of FMF patients and R202Qpolymorphism. CONCLUSION: The results of this study showed that there was a high association between MEFV gene R202Q polymorphism and FMF. R202Q polymorphism should be included in routine molecular diagnosis of FMF patients.