Anikó Folhoffer

Myocardial infarction is associated with Sp1 binding site polymorphism of collagen type 1A1 gene

Objective — Human atherosclerotic lesions contain collagen type 1, which plays a pivotal role in atherosclerotic plaque stability. In contrast, the normal coronary arteries do not express this type of collagen. Data have shown that the collagen type 1A1 (COL1A1) gene Sp1 binding site (-1245 G/T) polymorphism is associated with disturbed collagen protein production. Methods — In our study, COL1A1 gene Sp1 polymorphism was investigated in 136 patients with myocardial infarction (MI) 5 months after the acute phase, and 212 age-matched control subjects in association with any cardiovascular risk factors (such as serum adiponectin levels, hyperinsulinaemic status, hyperlipaemia). Results — The “SS” genotype of the COL1A1 gene was found to occur significantly more frequently in patients surviving a MI, as compared to the control group and the “Ss” and “ss” genotype frequencies (the presence of the s allele) were lower in our patients, than in control group. However, the occurrence of cardiovascular risk factors was significantly higher among the “s” allelic carriers as compared to patients carrying the “S” allele of the COL1A1 gene. Conclusion — Our results raise the possibility that COL1A1 gene Sp1 polymorphism might have an impact on the development of MI.

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis

Background/aim The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). Patients and methods Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. Results Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. Conclusions We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.

Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease

Objective. Wilsons disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost-effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilsons disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile) was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time-saving, and cost-effective method for diagnosing Wilsons disease in selected cases.

Disturbed post-movement beta synchronization in Wilson's disease with neurological manifestation

We analyzed the changes of post-movement beta synchronization (PMBS) of the electroencephalogram (EEG) in Wilsons disease with neurological manifestation. Our aim was to determine if PMBS in Wilsons disease is altered in a different way than in Parkinsons disease or in essential tremor. Our purpose was to find out whether the analysis of PMBS could help the diagnosis in ambiguous cases. Ten patients with neurological manifestation of Wilsons disease and ten controls performed self-paced movements with the dominant hand during EEG acquisition. Five electrodes above the sensorimotor cortex were selected for evaluation (C3, C1, Cz, C2, C4) as contralateral (C); contralateral medial (CM); medial (M); ipsilateral medial (IM); ipsilateral (I) relative to the dominant hand. Power and latency of PMBS were calculated by time resolved power spectral analysis with multitaper method. PMBS power in the C electrode position was significantly lower in patients than in controls, its contralateral preponderance disappeared in the patient group. In every location, latency of PMBS was significantly longer in the Wilson group compared to controls. More altered PMBS could be measured in patients with both basal ganglia and cerebellar involvements. Since decreased power of PMBS was observed in Parkinsons disease and increased latency in essential tremor, the combined change of PMBS can indicate pathology of different neural circuits and may help the diagnosis in challenging cases.