- MeSH
- časná diagnóza MeSH
- dítě MeSH
- hyperlipoproteinemie typ II * diagnóza farmakoterapie MeSH
- kongresy jako téma MeSH
- LDL-cholesterol analýza škodlivé účinky MeSH
- lidé MeSH
- náchylnost k nemoci MeSH
- plošný screening metody MeSH
- rizikové faktory MeSH
- statiny terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
BACKGROUND: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. METHODS: The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. RESULTS: The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1-4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. CONCLUSIONS: The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.
- MeSH
- genová přestavba MeSH
- hyperlipoproteinemie typ II * genetika epidemiologie MeSH
- lidé MeSH
- mutace MeSH
- receptory LDL genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.
- MeSH
- anticholesteremika * terapeutické užití MeSH
- ateroskleróza * farmakoterapie MeSH
- homozygot MeSH
- homozygotní familiární hypercholesterolemie * MeSH
- hyperlipoproteinemie typ II * diagnóza genetika terapie MeSH
- LDL-cholesterol genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- hyperlipoproteinemie typ II * diagnóza metabolismus patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
V súčasnosti existuje viacero hypotéz, podľa ktorých poruchy sluchu môžu byť asociované so závažnou hypercholesterolémiou, no dostupné literárne údaje zostávajú nateraz nejednoznačné. S novými odhadmi prevalencie familiárnej hypercholestrolémie sa toto ochorenie v bežnej populácii vyskytuje oveľa častejšie, ako sa donedávna predpokladalo. Napriek pár výnimkám je detekcia ochorenia nízka, keďže vo väčšine krajín sveta je stále diagnostikovaných menej ako 1 % pacientov z odhadovaného počtu chorých. Zároveň sme dnes svedkami nástupu prelomovej generácie hypolipidemických liekov, ktoré prinášajú dramatický pokles celkového cholesterolu (Total Cholesterol – T-C) a LDL-cholesterolu (LDL-C) a lepšie vyhliadky do budúcnosti nielen pre pacientov s vrodenými poruchami metabolizmu lipidov. O to väčšia je potreba týchto pacientov efektívne vyhľadávať a správne liečiť. Práve limitované dáta o asociácii hypercholesterolémie s poruchami sluchu podnecujú ďalší výskum v tejto oblasti.
There are currently several hypotheses that hearing loss may be associated with severe hypercholesterolemia, but the available literature remains ambiguous. With new estimates of the prevalence of familial hypercholesterolemia, the disease is much more common in the general population than previously thought. Although there are some exceptions, the detection rate of FH remains low, as it is still below 1 % in the most countries. At the same time, today we are witnessing the advent of a new generation of hypolipidemic drugs that bring a dramatic drop in total and LDL cholesterol and better prospects for the future, not only for patients with congenital disorders of lipid metabolism. The need for these patients to be effectively sought and treated correctly is all the greater. Limited data on the association of hypercholesterolemia with hearing impairment suggest further research in this area.
- MeSH
- humanizované monoklonální protilátky aplikace a dávkování MeSH
- hyperlipoproteinemie typ II * farmakoterapie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- PCSK9 inhibitory aplikace a dávkování MeSH
- percepční nedoslýchavost * etiologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- alirocumab,
- MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * farmakoterapie MeSH
- lidé MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dítě MeSH
- financování zdravotní péče MeSH
- hyperlipoproteinemie typ II prevence a kontrola MeSH
- kardiovaskulární nemoci * mortalita prevence a kontrola MeSH
- kongresy jako téma MeSH
- kontinuita péče o pacienty MeSH
- lidé MeSH
- plošný screening MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- sběr dat zákonodárství a právo MeSH
- systémy podporující rozhodování v léčbě trendy MeSH
- vytváření politiky MeSH
- zdravotní politika trendy MeSH
- zdravý životní styl MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- novinové články MeSH
- Geografické názvy
- Evropa MeSH
Lipoprotein apheresis (LA) is a therapeutic option for patients with severe hypercholesterolemia who have persistently elevated LDL-C levels despite attempts at drug therapy. MicroRNAs (miRNAs), important posttranscriptional gene regulators, are involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty preselected circulating miRNAs in patients under long-term apheresis treatment. Plasma samples from 12 FH patients (men = 50%, age = 55.3 ± 12.2 years; mean LA overall treatment time = 13.1 ± 7.8 years) were collected before each apheresis therapy every sixth month over the course of four years of treatment. Eight complete follow-up (FU) samples were measured in each patient. Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, miR-21, miR-126, miR-122, miR-26a, and miR-185; all p < 0.04) during FU were identified. Overall apheresis treatment time influenced circulating miR-146a levels (p < 0.04). In LDLR mutation homozygotes (N = 5), compared to heterozygotes (N = 7), we found higher plasma levels of miR-181, miR-126, miR-155, and miR-92a (all p < 0.03). Treatment with PCSK9 inhibitors (N = 6) affected the plasma levels of 7 miRNAs (miR-126, miR-122, miR-26a, miR-155, miR-125a, miR-92a, and miR-27a; all p < 0.04). Long-term monitoring has shown that LA in patients with severe familial hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer the treatment using LA, the better the miRNA milieu depicting the potential cardiovascular risk.
- MeSH
- cirkulující mikroRNA * genetika MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 genetika MeSH
- senioři MeSH
- separace krevních složek * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- familiární chylomikronemie, Inklisiran,
- MeSH
- apolipoprotein A-I biosyntéza farmakologie MeSH
- apolipoprotein C-III antagonisté a inhibitory MeSH
- deriváty kyseliny fibrové farmakologie MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- hypercholesterolemie * farmakoterapie MeSH
- hyperlipoproteinemie typ II komplikace parazitologie MeSH
- hypolipidemika * farmakologie terapeutické užití MeSH
- klinické zkoušky, fáze III jako téma MeSH
- PCSK9 inhibitory farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Publikační typ
- přehledy MeSH
