Malgorzata Bednarska-Makaruk

Institute of Psychiatry and Neurology · DEPARTMENT OF GENETICS

Almost all monogenic diseases of cholesterol metabolism are classified as rare (less than 1 in 2000 people) or ultra-rare with the exception of heterozygous familial hypercholesterolemia, which is a relatively common genetic disorder (1 in 250 individuals). These disorders are caused by numerous rare mutations in genes related to lipid metabolism....

We report on a 36-year-old man with cerebellar-extrapyramidal syndrome and severe heart failure because of dilated cardiomyopathy of unknown origin. Dysarthria and cardiac arrhythmia began at early childhood (4 years of age). Brain MRI (28 years of age) demonstrated severe cerebellar atrophy. At the age 32, he presented with dysarthria, ataxia, dys...

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial etiology. Genetic factors are believed to be significant in t...

Introduction: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The etiology of this disorder is multifactorial. Genetic factors which influence the predisposition to AN have...

Increased activity of dipeptidyl peptidase IV (DPP-IV) was reported earlier in patients with different types of mucopolysaccharidoses. DPP-IV (also known as CD26 lymphocyte T surface antigen) is a transmembrane protein showing protease activity. This enzyme displays various functions in the organism and plays an important role in multiple processes...

Changes in gene expression profiles were investigated in 23 patients with Niemann–Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3, THBS4), cytokine signalling (MMP3), extracellular matrix degradation...

Obesity has already been recognized as an important risk factor for Alzheimer disease and dementia, but the exact causal mechanisms are still largely unexplored and are subject to ongoing research. There is much evidence that adipocyte dysfunction seems to be involved. Adiponectin, the most widespread adipocyte-derived hormone, is inversely correla...

Most common reasons for pregnancy loss are chromosomal anomalies of the fetus. They are found in as much as half of the miscarriages. The standard technique for assessment of chromosomal abnormalities in spontaneously aborted fetuses has been karyotyping, however, it needs cell culture which is the most vulnerable element of a diagnostic process. A...

Objective: The empirical literature describes the role of the oxytocinergic system in emotion perception (EP). Variants in the oxytocin (OXT) and oxytocin receptor genes have been associated with mental disorders, including anorexia nervosa (AN), that are characterized by difficulties in socioemotional functioning. Our study aimed to examine wheth...

Gaucher disease (GD) is a rare inherited metabolic disease caused by pathogenic variants in the GBA1 gene. So far, the pathomechanism of GD was investigated mainly in animal models. In order to delineate the molecular changes in GD cells we analysed gene expression profile in cultured skin fibroblasts from GD patients, control individuals and, addi...

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hy...

The aim of the study was to determine the role of adiponectin, leptin and resistin in various types of dementia and to investigate their association with inflammatory markers, insulin resistance and abdominal obesity. In 205 patients with dementia [89 with Alzheimer’s disease (AD), 47 with vascular dementia (VaD), 69 with mixed dementia (MD)], 113...

The Val158Met catechol‐O‐methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test...

Background: A possible role of adipokines in the regulation of body weight in patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes encoding adiponectin and resistin in AN have not been widely assessed, yet. Objectives: 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T polymorphisms in adiponectin and RETN c....

Aim: The aim of this study was to analyze the influence of effective preconceptional testing for carrier status in women at risk for Duchenne and Becker muscular dystrophies (D/BMD) on the prenatal diagnosis. Methods: A retrospective analysis of 201 prenatal tests was performed in 169 Polish women at risk, in regard to time of testing for carrie...

Epigenetics (particularly DNA methylation) together with environmental and genetic factors, are key to understanding the pathogenesis of many diseases including dementia. Disturbances in DNA methylation have already been implicated in dementia. Homocysteine metabolism, with folate and vitamin B12 as essential cofactors, is integral to methylation p...

It has been recognized that the importance of Vitamin D far exceeds its long-known role in mineral homeostasis. In this review its importance in various normal and pathological processes such as muscle work, cardiovascular health, diabetes and some neurological diseases is briefly presented. In particular, the role of Vitamin D in brain functioning...

Objectives: Mucopolysaccharidoses (MPS) are a group of rare, inherited metabolic disorders which result from the lack of one of the lysosomal enzymes responsible for the degradation of glycosaminoglycans. Early recognition of MPS is important as it enables prompt implementation of enzyme replacement therapy (ERT). Dipeptidyl peptidase-IV (DPP-IV)...

Epigenetics (i.e. DNA methylation) together with the environmental and genetic factors are the key to understanding the pathogenesis of many diseases including dementia. Disturbances in DNA methylation have been already implicated in dementia. Homocysteine metabolism, with folate and vitamin B12 as essential cofactors, is integral to methylation pr...

The aim of the article is to review the current knowledge of mechanisms linking adipokines, insulin resistance and dementia. Adipose tissue secretes into the bloodstream a number of hormones named adipokines, which regulate many aspects of the metabolism and energy balance. They also play a role in blood pressure regulation, hemostasis and immunity...

Due to the increasing incidence of Alzheimer's disease (AD), many studies have aimed to improve its diagnosis. Particular attention has been focused on measuring volumes of brain structures. Only few studies have investigated whether the cerebellar volume changes with the stage of dementia. It is controversial whether the serum apolipoprotein E (Ap...

Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia - 136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T pol...

Metachromatic leukodystrophy (MLD) is a rare lysosomal disorder caused by deficient activity of arylsulfatase A or the lack of saposin B, which results in the accumulation of sulfatide in the oligodendrocytes and in the Schwann cells. Three main clinical types of MLD can be distinguished according to the age of onset and the dynamics of clinical ou...

Paraoxonase 1 (PON1) activity and metabolic syndrome traits were evaluated in 169 demented patients (81 recognized as AD, 32 as VaD, 56 as MD) and in 64 control individuals. Paraoxonase activity was determined spectrophotometrically using phenyloacetate as substrate. Metabolic syndrome was recognized according to AHA/NHLBI criteria. In the whole gr...

Objectives. Co-occurrence of metabolic syndrome features and dementia was studied. Methods. In 151 demented patients and 64 control individuals the presence of metabolic syndrome was diagnosed according to the modified Grundy et al. criteria (hypertension, obesity, high triglyceride and low high density lipopoprotein (HDL) cholesterol serum levels,...

Cholesterol ester storage disease (CESD) is a recessive disorder due to deficient activity of lysosomal acid lipase leading to lysosomal accumulation of cholesterol esters and triglycerides. Its prevalence in the Polish population is unknown. Clinical manifestation includes hepatomegaly (usually mild at onset) with hypercholesterolemia (hyperlipide...

Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the m...

Paraoxonase activity, homocysteine level and lipids were determined in 120 patients with dementia (51 with Alzheimer disease, 28 with dementia of vascular origin, 41 with mixed dementia), 45 with mild cognitive impairment and in 61 age and sex matched controls without dementia. Paraoxonase activity was decreased in Alzheimer disease and in mixed de...

In serum of 114 patients with dementia and of 102 controls the level of IG class immunoglobulins directed against oxidized LDL and lipids were determined. In isolated DNA apolipoprotein E gene (APOE) polymorphism was identified. In some individuals very high levels of the antibodies were observed. exceeding the 90 percentile in the investigated gro...

Vascular cognitive impairment is an important cause of cognitive decline in the elderly. Ischemic lesions in the brain have an influence on the natural history of dementia. Vascular dementia can be caused by small-vessels disease (S-VaD) or by large-artery atherosclerosis with vascular lesions in strategic areas of the brain (M-VaD). In both cases...

Objective. To assess polymorphism of the 5-HT2A serotonin receptor gene promoter (-1438 G/A) in patients with seasonal affective disorder (winter depression). Method. The rates of the 5-HT2A promoter (-1438 G/A) polymorphism in a group of 29 patients with seasonal affective disorder (SAD), 32 depressive inpatients with non seasonal affective disord...

Infants with chronic cholestasis may require parenteral nutrition with lipid emulsions to provide energy and essential fatty acids but the optimal strategy is controversial. We studied the effects of parenteral lipid emulsions with long-chain triacylglycerols (LCTs) or a mixture of LCTs and medium-chain triacylglycerols (MCTs/LCTs) on serum bilirub...

In 229 patients with dementia and in 144 control subjects, polymorphisms of apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein, alpha(2)-macroglobulin, interleukin (IL) 1beta, angiotensin-converting enzyme and of methylene tetrahydrofolate reductase genes were investigated. In plasma, antibodies against Chlamydia pneumo...

The paper presents current opinions on the mechanism of beta-amyloid accumulation, the role of cholesterol in the pathogenesis of dementia and observations of the role of statins in its development. Most of the observations were done on Alzheimer's disease, some of them concerned also dementia of a vascular origin and cognition. Statins are inhibit...

To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression...

The aim of the work was to recognize whether often observed high levels of apolipoprotein (a) [Lp(a)] in patients shortly after an ischemic stroke are a result of the acute phase reaction. In 13 patients Lp(a) was determined within the first 24 hours after the stroke onset, after the next 7 days and after three months i.e. when it could be consider...

Spinocerebellar ataxias are a group of neurodegenerative disorders caused by dynamic mutations of microsatellite repeats. Two novel forms of SCAs have been described recently: SCA8, with expansions of CTA/CTG repeats in 3'UTR of the SCA8 gene, and SCA12, caused by expansion of the CAG tract in 5'UTR of the SCA12/PP2R2B gene. Analysis of CTA/CTG and...

In patients with dementia, 29 diagnosed as probably suffering from Alzheimer's disease and 46 subjects with dementia of vascular origin, and in 41 non demented control subjects LDL oxidation in vitro was compared in carriers of various apolipoprotein E alleles. Restriction isotyping was performed by gene amplification and cleavage with Hhal, LDL ox...

Little is known about the role of antioxidant activity in the pathogenesis of stroke-associated neuronal damage and impairment following a stroke. Increased free radical formation together with reduced antioxidant defense may increase neuronal injury. A low concentration of antioxidants such as alpha-tocopherol may influence the development of post...

The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs) by murine peritoneal macrophages is described and compared with the uptake of acetylated LDLs. The fluorescent marker DiI was used. No competition between ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not inhibited by polyinosinic acid or fucoidin...

The prevalence of the familial defective apolipoprotein B-100 (FDB) Arg3500Gln mutation in 525 unrelated hypercholesterolaemic Polish subjects was evaluated. DNA samples were screened for FDB mutation using SSCP method. Presence of mutation was confirmed using a mismatch MspI PCR strategy. Plasma lipid levels and clinical characteristics of 13 pati...

Genotype of apolipoprotein E has been identified in a group of randomly selected Polish subjects participating in a cross-sectional study performed within the POL-MONICA Program, the part of international study WHO-MONICA Project. The investigated group consisted of 170 persons, 92 males and 78 females aged 41-69 years (mean age 62.0+/-5.11). The o...

The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the patients three months after the onset of ischaemic stroke. A group of 56 patients was investigated. Stroke was diagnosed as caused by atherosclerotic changes in main cerebral arteries in 32 patients and in 11 by changes in cervical arteries. In 13 persons a lacunar strok...

In 64 individuals with dementia (26 Alzheimer type, 34 of vascular origin and 4 other types of dementia) apolipoprotein E genotype was identified. Frequency of epsilon4 allele was 36.5% in Alzheimer patients and 32.4% in vascular dementia ones. In a group of 39 nondemented individuals of the same age the epsilon4 frequency was 11.5%. In demented pa...

In 31 alcohol addicted patients entering detoxication treatment and in 14 social drinkers apolipoprotein E (Apo E) was assayed by radial immunodiffusion in the whole serum and after phosphotungstate Mg2+ precipitation. Serum Apo E level in the intoxicated individuals was increased compared with the controls. The Apo E increase was mostly due to the...

The effect of six months' treatment with bezafibrate (400-600 mg daily) on serum lipids, lipoproteins and apolipoproteins concentrations was investigated in 32 patients with primary hyperlipoproteinemia (HLP) type IIa, IIb and IV. In all types of HLP the reduction of serum cholesterol (CH), triglycerides (TG), very low density lipoprotein (VLDL) fr...

A comparative studies on the effect of propranolol and acebutolol on blood pressure, cardiac function, blood serum lipids and lipoproteins were carried out in 48 patients with the primary hypertension double-blind method was applied. Tested drugs were given for 12 weeks. It was found, that both drugs are potent and comparable hypotensive agents nor...