Analiza polimorfizmów -11391G>A oraz +45T>G genu ADIPOQ u kobiet z nadmiernym przyrostem masy ciała w ciąży

Objectives: The aim of our study was to evaluate the frequency of genotypes and alleles of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene in Polish women with excessive weight gain during pregnancy. A possible correlation between these polymorphisms and selected clinical and anthropometric parameters has been analyzed. Material and methods: A total of 153 pregnant Caucasian women of Polish origin with normal pre-pregnancy body mass were analyzed: 78 women with excessive weight gain (study group) and 75 women with normal weight gain during pregnancy (control group). The analysis of the polymorphisms was performed by PCR/RFLP. Results: The influence of the -11391G>A polymorphism on body mass and BMI values at the end of pregnancy (pG polymorphism with body mass at the end of pregnancy and pre-pregnancy WHR values (pA polymorphism on the parameters assessed at the end of pregnancy (BMI and body mass), suggests a protective role of the -11391A genetic variant in excessive weight gain. It is claimed that the mutated +45G allele of the +45T>G ADIPOQ polymorphism shows a possible connection with higher pre-pregnancy WHR values and body mass at the end of pregnancy. Our findings suggest a possible contribution of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene to the pathomechanism of excessive weight gain in pregnant women from the Polish population. This observation should be confirmed in a larger sample size study.Cel pracy: Celem pracy była ocean częstości występowania genotypów i alleli polimorfizmu -11391G>A oraz +45T>G genu ADIPOQ u kobiet z nadmiernym przyrostem masy ciała w ciąży w populacji polskiej. Zbadano również korelację obydwu polimorfizmów z wybranymi parametrami klinicznymi i antropometrycznymi. Materiały i metody: Badaniem objęto 153 kobiety ciężarne rasy kaukaskiej z prawidłową masą ciała: 78 kobiet z nadmiernym oraz 75 kobiet z prawidłowym przyrostem masy ciała w ciąży stanowiących grupę kontrolną. Analizę badanych polimorfizmów przeprowadzono z wykorzystaniem metody PCR/RFLP. Wyniki: Odnotowano wpływ polimorfizmu -11391G>A na masę ciała i wartość BMI pod koniec ciąży (pG z masą ciała pod koniec ciąży i wartość WHR przed ciążą (pA na parametry badane po koniec ciąży: wskaźnik BMI oraz masę ciała, sugeruje protekcyjną rolę wariantu -11391A na nadmierny przyrost masy ciała. Potwierdzono, że zmutowany allel +45G polimorfizmu +45T>G wykazuje możliwy związek z większą wartością WHR przed ciążą oraz masą ciała pod koniec ciąży. Uzyskane wyniki sugerują możliwy udział polimorfizmów -11391G>A oraz +45T>G genu ADIPOQ z w patomechanizmie nadmiernego przyrostu masy ciała u ciężarnych kobiet z populacji polskiej. Obserwacja ta powinna być potwierdzona w większej liczebnie grupie pacjentek

Polimorfizm białka morfogenetycznego kości (BMP2) a etiologia osteoporozy

Objectives: Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to superfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. The aim: The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. Material and methods: Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. Results: In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. Conclusions: The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.Wstęp: Osteoporoza jest przewlekłą, uogólnioną chorobą kości uwarunkowaną przez wiele czynników, wśród których istotną rolę odgrywa podłoże genetyczne. Białko morfogenetyczne kości (BMP2 – bone morphogenetic protein), będące czynnikiem wzrostu należącym do nadrodziny białek TNF-, jest czynnie włączone w metabolizm tkanki kostnej. Białko BMP2 wykazuje potencjał osteoindukcyjny oraz reguluje wzrost płytki chrzęstnej, a tym samym bezpośrednio wpływa na proces osteogenezy. Cel pracy: Celem pracy była analiza częstości występowania genotypów i alleli polimorfizmu 570A>T oraz 5375G>A genu BMP2 w populacji kobiet polskich po menopauzie, jak również określenie związku między badanymi wariantami polimorficznymi a parametrami obrotu kostnego. Materiał i metody: Badaniem objęto 117 niespokrewnionych kobiet rasy kaukaskiej po menopauzie (średni wiek 55,1 lat), zamieszkujących region Wielkopolski. Analizę polimorfizmów 570A>T oraz 5375G>A genu BMP2 przeprowadzono z wykorzystaniem metody reakcji łańcuchowej polimerazy/polimorfizmu długości fragmentów restrykcyjnych (PCR/RFLP – polymerase chain reaction/restriction fragment lenght polymorphism), natomiastpomiar gęstości mineralnej kości (BMD – bone mineral density) wykonano z zastosowaniem metody DEXA. W badaniu analizowano również wybrane parametry kliniczne oraz parametry obrotu kostnego. Wyniki: Dla obydwu polimorfizmów 570A>T oraz 5375G>A genu BMP2 odnotowano porównywalną częstość występowania genotypów i alleli w badanych grupach kobiet po menopauzie z osteopenią, osteoporozą oraz prawidłową wartością T-score. Analiza nie pokazała również związku parametrów klinicznych oraz obrotu kostnego z poszczególnymi genotypami polimorfizmów BMP2 u kobiet z osteoporozą, osteopenią oraz w grupie z prawidłową wartością T-score. Wnioski: W pracy nie potwierdzono bezpośredniego związku polimorfizmów 570A>T oraz 5375G>A genu BMP2 z rozwojem osteoporozy w populacji kobiet polskich po menopauzie. Badania wskazały również na brak korelacji polimorfizmów 570A>T oraz 5375G>A genu BMP2 z analizowanymi parametrami klinicznymi oraz parametrami obrotu kostnego

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Work patterns and a tendency among Polish nurses to leave their job

Background Work patterns are important factors in employees’ decisions to change their job or leave their profession. The majority of nurses in Poland are women who play other social roles besides work. For this reason, satisfaction with their work patterns including input into work schedules, has a particularly significant impact on considering the idea of quitting their job. Material and Methods The study was conducted in 2008–2011 in 8 out of 10 higher education institutions which train nurses. Data obtained from 1045 questionnaires collected from a total of 1049 respondents from 3 randomly selected higher education institutions was used in this research paper. The relationship between the qualitative features and dichotomus quality features under examination was assessed using univariate and multivariate logistic regression models. Results The results of the univariate logistic regression indicate that the risk of quitting increases to the highest extent with a mixed work pattern; it is lower for 12/24 h, and slightly lower for 2 day/night shifts. Conclusions A pattern with a single day shift was adopted as the reference level to reduce the risk of Polish nurses’ quitting their job. Med Pr. 2018;70(2):145–5

ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare recessive disease with a prevalence of 1/10,000; its symptoms are caused by a kinetic dysfunction of motile cilia in the respiratory epithelium, flagella in spermatozoids, and primary cilia in the embryonic node. PCD is genetically heterogeneous: genotyping the already known PCD-related genes explains the genetic basis in 60-65% of the cases, depending on the population. While identification of new genes involved in PCD pathogenesis remains crucial, the search for new, population-specific mutations causative for PCD is equally important. The Slavs remain far less characterized in this respect compared to West European populations, which significantly limits diagnostic capability. The main goal of this study was to characterize the profile of causative genetic defects in one of the PCD-causing genes, ZMYND10, in the cohort of PCD patients of Slavic origin. The study was carried out using biological material from 172 unrelated PCD individuals of Polish origin, with no causative mutation found in nine major PCD genes. While none of the previously described mutations was found using the HRM-based screening, a novel frameshift mutation (c.367delC) in ZMYND10, unique for Slavic PCD population, was found in homozygous state in two unrelated PCD patients. Immunofluorescence analysis confirmed the absence of outer and inner dynein arms from the ciliary axoneme, consistent with the already published ZMYND10-mutated phenotype; cDNA analysis revealed the lack of ZMYND10 mRNA, indicating nonsense-mediated decay of the truncated transcript

Transmission electron microscope analysis.

<p>Right panel, outer and inner dynein arms (ODA and IDA, black arrows) in the cross-section of cilia from the respiratory epithelium of a healthy individual. Left panel, lack of ODA and IDA (white arrows) in patient #683. Magnification 30,000; lower panel—enlarged view of a single cilium. Black scale bars represent 0,1 μm.</p

cDNA analysis.

<p>The multiplex PCR was carried out with the use of primer pairs located in the exons of <i>ZMYND10</i> (expected product length 152 bp), <i>LRRC6</i> (224 bp), <i>CFTR</i> (301 bp) and <i>GAPDH</i> (382 bp). PCR amplification products were separated on 4% NuSieve agarose gel (FMC BioProducts) in TBE buffer. M1: 25 bp ladder (Fermentas); M2: 1 kb ladder (LifeTechnologies), P: patient #683; C: healthy control; 0: blank control with water as a template. An arrow indicates the expected position of ZMYND10 product in patient #683.</p

Potential miRNA target sites in <i>ZMYND10</i> mRNA.

<p>Potential miRNA target sites predicted using miRDB (database tab: ‘<i>Custom Prediction; Search for unconventional target sites in the coding region or 5'-UTR</i>’) are shown in the mRNA sequence downstream from the c.367delC mutation (spliced exons 4–12 in transcript 001 are shown in alternating blue and black colors; the site of the mutation is double underlined; position of the STOP codons—normal and premature—are underlined in bold). Seed sequences complementary to the highest scoring miRNAs (sequences shown below) are highlighted.</p

Localization of the c.367delC mutation and primers used to analyze <i>ZMYND10</i> exon 4.

<p>Upper panel—exon structure of the <i>ZMYND10</i> gene; lower panel—exon 4; an asterisk indicates position of the homozygous mutation found in patients #683 and #810; the short arrows depict approximate localization of the primers (forward and reverse) used for HRM and SSCP analysis</p

High-resolution immunofluorescence analysis of the subcellular localization of the ciliary ultrastructure markers.

<p>αβ-tubulin (red; in A) or acetylated α-tubulin (green; in B, C) were markers of microtubules; DNAH5 (green, in A) and DNAI2 (green, in B)–of outer dynein arms; DNALI1 (red, in C)–of inner dynein arms; CCDC39 (red, in D)–of nexin-dynein regulatory complex, and LRRC6 (red, in E)–of cytoplasmic assembly complex. DIC, differential interference contrast; nuclei were stained with Hoechst 33342 (blue). Respiratory epithelium cells from the control and from patient #683 are shown in upper and lower panels, respectively. White scale bars represent 10 μm.</p