Sırrı Çam

Polymorphisms of the methylenetetrahydrofolate reductase, vascular endothelial growth factor, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 and apolipoprotein E genes are not associated with carotid intima-media thickness.

BACKGROUND Single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), monocyte chemoattractant protein-1 (MCP-1) and apolipoprotein E (ApoE) genes appear to be a genetic risk factor for atherosclerosis. Common carotid intima-media thickness (cIMT) provides information on the severity of atherosclerosis. OBJECTIVE To investigate the relationship between cIMT and gene polymorphisms associated with atherosclerosis in Turkish patients with coronary artery disease (CAD). METHODS Sixty-two patients with angiographically diagnosed stable CAD were divided into two groups according to their cIMT values (group 1: n=35, cIMT of 1 mm or greater; group 2: n=27, cIMT of less than 1 mm). MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE (E2, E3 and E4) gene polymorphisms (where A is adenine, C is cytosine, G is guanine and T is thymine) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Evaluations of cardiovascular risk factors and coronary atherosclerotic lesions were performed in all patients. Serum homocysteine and high-sensitivity C-reactive protein were measured and compared between the two groups. RESULTS Serum high-sensitivity C-reactive protein (P=0.04) and homocysteine (P=0.006) levels were higher in group 1 than in group 2. The ratio of multivessel CAD and previous myocardial infarction was significantly higher in group 1 than in group 2 (P=0.014). In the study population, no significant difference in cIMT was observed according to the polymorphisms studied. Only hyperhomocysteinemia (OR 1.17 [95% CI 1.01 to 1.35], P=0.033) and previous myocardial infarction (OR 3.76 [95% CI 1.10 to 12.81], P=0.034) maintained a significant correlation with cIMT on multiple logistic regression analysis. CONCLUSION cIMT is increased in patients with hyperhomocysteinemia, inflammation and extended CAD. MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE single nucleotide polymorphisms were not associated with increased cIMT.

Effect of monocyte chemoattractant protein‐1 (MCP‐1) gene polymorphism in Turkish patients with premature coronary artery disease

Objectives. It has been suggested that monocyte chemoattractant protein‐1 (MCP‐1) is important in the initiation of atherosclerosis and crucial in monocyte recruitment into the subendothelial lesions. Recent studies have demonstrated that MCP‐1 −2518 A>G polymorphism is associated with susceptibility to coronary artery disease (CAD). Since there are conflicting reports on the possible association of MCP‐1 −2518 A>G polymorphism with CAD, we investigated the role of this polymorphism in Turkish patients with premature CAD. Material and methods. Genomic DNA was collected from 171 premature CAD patients and 151 healthy individuals. MCP‐1 −2518 A>G polymorphism was genotyped using the PCR‐RFLP method. Results. There were no differences between genotype distribution and allele frequencies in the premature CAD and control groups (AA: 49.7 %; AG: 40.3 %; GG: 10.0 % in premature CAD groups and AA: 53.7 %; AG: 34.4 %; GG: 11.9 % in controls; p = 0.53). The prevalence of the G allele was 0.302 in patients and 0.291 in controls. Conclusions. Our data demonstrate that MCP‐1 −2518 A>G polymorphism is not associated with premature CAD in Turkish patients. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of CAD in various populations.

Comprehensive analysis of a large-scale screen for MEFV gene mutations: do they truly provide a "heterozygote advantage" in Turkey?

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781-amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.

Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study

Abstract Objective: Gestational diabetes mellitus (GDM) is characterized with insulin resistance which is diagnosed during pregnancy. Although pregnancy is a diabetogenic state, not all women develop GDM. Genetic factors together with enviromental factors cause the maladaptation of maternal pancreas to this diabetogenic state and GDM develops. ADAMTS-9 is a recently recognized molecule whose genetic variants have risk of GDM. Decreased levels have already been shown in fetal membranes. Maternal serum levels of this protein have not been studied yet. We hypothesized that the alteration of ADAMTS-9 expression should cause changes in maternal serum levels which further could help to identify the disease and develop new treatment strategies. Materials and methods: This prospective case–control study is consisted of 27 pregnancies with GDM and 30 healthy singleton pregnancies matched for matenal age, gestational week, and maternal weight. GDM diagnosis was made with 2-h 75 g oral glucose tolerance test. ADAMTS-9 levels were compared between groups. Results: ADAMTS levels were 3.62 ± 0.33 ng/dL (range: 3.04–4.23) in GDM group and 4.65 ± 1.70 ng/dL (range: 3.07–8.21) in control group (p < 0.001). ADAMTS levels were not affected by maternal age, gestational age, and maternal weight. Conclusion: ADAMTS-9 levels were significantly lower in GDM pregnancies. This may help to understand the mechanism of GDM pathogenesis. In future, target treatments with ADAMTS proteins may help to improve the severity of diabetes pathogenesis.

Amniocentesis results of Manisa tertiary care in 2012

Objective: The aim of this study was to evaluate the results of invasive amniocentesis procedures performed for karyotype analyzing in our clinic in 2012. Methods: The data of 83 cases, to whom performed amniocentesis for karyotype analyzing by reason of first trimester screening test’s increased risk (≥1/270), second trimester screening test’s increased risk (≥1/270), determination of abnormality with ultrasound and other causes, was analyzed retrospectively in 2012. Results: Eighty of 83 amniocentesis procedures performed were successful in tissue culture. Culture success rate in amniocentesis was determined as 96.4%. Chromosomal abnormality was determined as 10% of these cases (8/80). The most common indication of amniocentesis was second trimester screening test’s increased risk. Amniocentesis was performed to 30 cases for second trimester screening test’s increased risk and chromosomal abnormality was determined in two cases (6.6%). The second indication for amniocentesis was increased risk of first trimester screening test which was 34.9% (29/83). Chromosomal abnormality was found in 13.8% of these cases (4/29). The other indications were the determination of abnormality during ultrasonography as 15.6%, family request as 9.6%, increased quadruple screening test as 2.4%, and history of delivery with chromosomal abnormality as 2.4%. No complication was seen after amniocentesis in all 83 cases. Conclusion: Amniocentesis is the most applicable, with the least complication and the oldest prenatal diagnosis procedure in practice. Although chorionic villus sampling is first diagnosis test after first trimester screening test practically, pregnant women could come to reference centers like our hospital for different reasons after 14 weeks of gestation. Therefore, increased risk of first trimester screening test is determined as a high rate indication for amniocentesis in our center.

The Relationship Between Angiotensin Converting Enzyme Insertion/deletion Polymorphism and Age-related Macular Degeneration

Background: To assess the role of serum angiotensin converting enzyme (ACE) levels and ACE insertion /deletion (I/D) genetic polymorphism in Turkish age-related macular degeneration (AMD) patients and control subjects. Methods: This prospective study consisted of 78 patients with AMD and 68 control subjects. The I/D polymorphism of the ACE was carried out by polymerase chain reaction. Serum ACE levels were determined by using the ELISA method. Results: There was no significant difference in the mean serum values of ACE between the control and patient groups (p = 0.107). The genotypic frequencies of ACE polymorphism in the control and patient groups were not significantly different either (p = 0.218). Conclusion: We could not show a significant role of serum ACE levels and ACE I/D genetic polymorphism in the etiopathogenesis of AMD in the Turkish population, and our findings did not support the idea that serum ACE levels and ACE DD genotype were risk factors for AMD.