BACKGROUND: Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease (CAD) that is characterized by concentric fibrous intimal hyperplasia along the length of coronary vessels, and is recognized as long-term complication after heart transplantation. The chromosomal loci 9p21, 6q25.1, and 2q36.3, represented by their respective leading variants rs10757274, rs6922269 and rs2943634, have been linked with a history of CAD by genome-wide association studies. We aimed to investigate the associations of genetic variants at the loci 9p21, 6q25.1, and 2q36.3 with CAV as genetic risk factors for early prediction. METHODS: Genomic DNA was extracted from paired aortic samples of 727 heart recipients (average age 50.8 ± 12.2 years; 21.3% women) and corresponding donors (average age 39.7 ± 12.0 years; 26.1% women). The variants within the loci 9p21, 6q25.1, and 2q36.3 were genotyped using PCR-RFLP. RESULTS: The recipients' variants of 9p21 (OR 1.97; 95% CI, 1.21-3.19 for GG vs. +A comparison, p = 0.0056) and 2q36.3 (OR 2.46; 95% CI, 1.12-6.17 for +C vs. AA comparison, p = 0.0186) were associated with higher incidence of CAV during the first year following heart transplantation. No such association was found for donor genotypes. CONCLUSIONS: Our data suggest that variants at the locus 9p21 (rs10757274) and 2q36.3 (rs2943634) are associated with early CAV development.

• Klíčová slova
• SNPs, cardiac allograft vasculopathy, transplantation,
• MeSH
• alografty * MeSH
• celogenomová asociační studie MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 2 genetika   MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• lidské chromozomy, pár 9 genetika   MeSH
• nemoci koronárních tepen * genetika   patologie   etiologie   MeSH
• transplantace srdce * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor Klotho gene and Klotho protein in the immunopathogenesis of gliomas. We examined Klotho genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method. We found a statistically significantly increased frequency of rs1207568A allele and rs1207568 GA genotypes in co-dominant, dominant and over-dominant models in grade IV as compared to grade II and III glioma patients. The levels of soluble α Klotho (sαKL) were significantly lower in grade III and IV glioma patients than in healthy controls (p = 0.034; 0.0083). Patients with sαKL levels above 2500 pg/mL survived significantly longer than patients with sαKL below 2500 pg/mL (p = 0.038). We also found a positive correlation of the serum levels of sαKL with seven biomarkers, like angiogenic vascular endothelial growth factor (p = 0.0008), chemokine fractalkine (p = 0.0009), interferon γ (p = 0.003), glial derived neurotrophic factor (p = 0.0268), pro-inflammatory and pro-Th1 cytokine IL-6 (p = 0.0347), anti-inflammatory, pro-Th2 cytokines IL-4 (p = 0.0037) and IL-13 (p = 0.0004). Our results suggest the impact of Klotho genetic variants and Klotho levels on advanced-grade glioma.

• Klíčová slova
• Klotho gene, cytokines, glioma, inflammation, overall survival, α klotho,
• MeSH
• cytokiny * krev   genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• gliom * genetika   krev   mortalita   patologie   MeSH
• glukuronidasa * krev   genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory mozku * genetika   krev   mortalita   patologie   MeSH
• proteiny Klotho * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň nádoru * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny * MeSH
• glukuronidasa * MeSH
• nádorové biomarkery MeSH
• proteiny Klotho * MeSH

OBJECTIVES: COVID-19 caused a global pandemic with millions of deaths. Fat mass and obesity-associated gene (FTO) (alias m6A RNA demethylase) and its functional rs17817449 polymorphism are candidates to influence COVID-19-associated mortality since methylation status of viral nucleic acids is an important factor influencing viral viability. METHODS: We tested a population-based cohort of 5233 subjects (aged 63-87 years in 2020) where 70 persons died from COVID-19 and 394 from other causes during the pandemic period. RESULTS: The frequency of GG homozygotes was higher among those who died from COVID-19 (34%) than among survivors (19%) or deaths from other causes (20%), P <0.005. After multiple adjustments, GG homozygotes had a higher risk of death from COVID-19 with odds ratio = 2.01 (95% confidence interval; 1.19-3.41, P <0.01) compared with carriers of at least one T allele. The FTO polymorphism was not associated with mortality from other causes. CONCLUSIONS: Our results suggest that FTO variability is a significant predictor of COVID-19-associated mortality in Caucasians.

• Klíčová slova
• COVID-19, FTO, Mortality, Polymorphism, SARS-CoV-2,
• MeSH
• alely MeSH
• COVID-19 * mortalita   genetika   virologie   MeSH
• gen pro FTO * genetika   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• SARS-CoV-2 fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FTO protein, human MeSH Prohlížeč
• gen pro FTO * MeSH

BACKGROUND: The associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors. METHODS: In a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391). RESULTS: In 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol - LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene. CONCLUSION: In addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.

• Klíčová slova
• Cardiovascular risk factors, Gene for connexin 37, Sex, Type 1 diabetes mellitus, Vascular parameters,
• MeSH
• diabetes mellitus 1. typu * genetika   patofyziologie   MeSH
• diabetické angiopatie genetika   patofyziologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• fotopletysmografie MeSH
• genetická predispozice k nemoci MeSH
• hodnoty glomerulární filtrace MeSH
• intimomediální šíře tepenné stěny MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• protein alfa 4 mezerového spoje * genetika   MeSH
• průřezové studie MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• sexuální faktory MeSH
• tlakový index kotník-paže MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gap junction protein alpha 4, human MeSH Prohlížeč
• protein alfa 4 mezerového spoje * MeSH

BACKGROUND: The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. METHODS: To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. RESULTS: Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. CONCLUSIONS: We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

• Klíčová slova
• Caucasians, apolipoprotein L1, cardiovascular disease, mortality, polymorphism,
• MeSH
• akutní koronární syndrom * genetika   MeSH
• apolipoprotein L1 * genetika   MeSH
• apolipoproteiny genetika   MeSH
• běloši genetika   MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny HDL genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• APOL1 protein, human MeSH Prohlížeč
• apolipoprotein L1 * MeSH
• apolipoproteiny MeSH
• lipoproteiny HDL MeSH

The Palaearctic species of Aphodius Hellwig, 1798, subgenus Liothorax Motschulsky, 1860 are revised using a combination of chromosome analysis, molecular phylogenetics and morphological statistical analysis. Sixteen species are recognised, one of which is shown to comprise two subspecies. Based mainly on the morphology of the aedeagal endophallus and the phylogenetic analysis, they are placed in two groups: the. niger group, apparently monophyletic, comprising Aphodius (Liothorax) niger Illiger, 1798, A. (L.) muscorum (Ádám, 1994), stat. rest., A. (L.) felixsp. nov., A. (L.) bellumgerenssp. nov., A. (L.) bameulisp. nov., A. (L.) krellisp. nov., A. (L.) isikdagensis (Balthasar, 1953), A. (L.) albertisp. nov. and A. (L.) wilsonae Maté et Angus, 2005, stat. rest.; and the plagiatus group, almost certainly paraphyletic, comprising A. (L.) plagiatus (Linnaeus, 1767), including A. (L.) p. plagiatus and A. (L.) p. sinoplagiatussubsp. nov., A. (L.) rodrigoisp. nov., A. (L.) discoidesA. Schmidt, 1916, stat. rest., A. (L.) rutilipennis (Baudi di Selve, 1870), stat. rest., A. (L.) chellalasp. nov., A. (L.) kraatzi Harold, 1868, and A. (L.) rusakovi Gusakov, 2004. A key to the species is given as well as details of their morphology, distributions, and habitats.

• Klíčová slova
• Chromosomes, Scarabaeidae, distribution, habitats, morphology, mtDNA, new species, taxonomy,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

• Klíčová slova
• Acute coronary syndrome, Cholesterol, Polymorphism, Risk estimation,
• MeSH
• akutní koronární syndrom * genetika   MeSH
• cholesterol MeSH
• genetické rizikové skóre * MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• cholesterol MeSH

BACKGROUND: Long-term environmental exposure to metals leads to epigenetic changes and may increase risks to human health. The relationship between the type and level of metal exposure and epigenetic changes in subjects exposed to high concentrations of metals in the environment is not yet clear. The aim of our study is to find the possible association of environmental long-term exposure to metals with DNA methylation changes of genes related to immune response and carcinogenesis. We investigated the association of plasma levels of 21 essential and non-essential metals detected by ICP-MS and the methylation level of 654 CpG sites located on NFKB1, CDKN2A, ESR1, APOA5, IGF2 and H19 genes assessed by targeted bisulfite sequencing in a cohort of 40 subjects living near metal mining area and 40 unexposed subjects. Linear regression was conducted to find differentially methylated positions with adjustment for gender, age, BMI class, smoking and metal concentration. RESULTS: In the metal-exposed group, five CpGs in the NFKB1 promoter region were hypomethylated compared to unexposed group. Four differentially methylated positions (DMPs) were associated with multiple metals, two of them are located on NFKB1 gene, and one each on CDKN2A gene and ESR1 gene. Two DMPs located on NFKB1 (chr4:102500951, associated with Be) and IGF2 (chr11:2134198, associated with U) are associated with specific metal levels. The methylation status of the seven CpGs located on NFKB1 (3), ESR1 (2) and CDKN2A (2) positively correlated with plasma levels of seven metals (As, Sb, Zn, Ni, U, I and Mn). CONCLUSIONS: Our study revealed methylation changes in NFKB1, CDKN2A, IGF2 and ESR1 genes in individuals with long-term human exposure to metals. Further studies are needed to clarify the effect of environmental metal exposure on epigenetic mechanisms and pathways involved.

• Klíčová slova
• CDKN2A, DNA methylation, ESR1, Environmental exposure, IGF2, NFKB1, Toxic metal, Uranium,
• MeSH
• epigeneze genetická * MeSH
• karcinogeneze genetika   MeSH
• kovy * škodlivé účinky   MeSH
• lidé MeSH
• metylace DNA * MeSH
• NF-kappa B - podjednotka p50 genetika   MeSH
• tumor supresorové geny MeSH
• vystavení vlivu životního prostředí * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kovy * MeSH
• NF-kappa B - podjednotka p50 MeSH
• NFKB1 protein, human MeSH Prohlížeč

BACKGROUND: Morphological and traditional genetic studies of the young Pliocene genus Hyles have led to the understanding that despite its importance for taxonomy, phenotypic similarity of wing patterns does not correlate with phylogenetic relationship. To gain insights into various aspects of speciation in the Spurge Hawkmoth (Hyles euphorbiae), we assembled a chromosome-level genome and investigated some of its characteristics. RESULTS: The genome of a male H. euphorbiae was sequenced using PacBio and Hi-C data, yielding a 504 Mb assembly (scaffold N50 of 18.2 Mb) with 99.9% of data represented by the 29 largest scaffolds forming the haploid chromosome set. Consistent with this, FISH analysis of the karyotype revealed n = 29 chromosomes and a WZ/ZZ (female/male) sex chromosome system. Estimates of chromosome length based on the karyotype image provided an additional quality metric of assembled chromosome size. Rescaffolding the published male H. vespertilio genome resulted in a high-quality assembly (651 Mb, scaffold N50 of 22 Mb) with 98% of sequence data in the 29 chromosomes. The larger genome size of H. vespertilio (average 1C DNA value of 562 Mb) was accompanied by a proportional increase in repeats from 45% in H. euphorbiae (measured as 472 Mb) to almost 55% in H. vespertilio. Several wing pattern genes were found on the same chromosomes in the two species, with varying amounts and positions of repetitive elements and inversions possibly corrupting their function. CONCLUSIONS: Our two-fold comparative genomics approach revealed high gene synteny of the Hyles genomes to other Sphingidae and high correspondence to intact Merian elements, the ancestral linkage groups of Lepidoptera, with the exception of three simple fusion events. We propose a standardized approach for genome taxonomy using nucleotide homology via scaffold chaining as the primary tool combined with Oxford plots based on Merian elements to infer and visualize directionality of chromosomal rearrangements. The identification of wing pattern genes promises future understanding of the evolution of forewing patterns in the genus Hyles, although further sequencing data from more individuals are needed. The genomic data obtained provide additional reliable references for further comparative studies in hawkmoths (Sphingidae).

• Klíčová slova
• Aristaless, Chromosome-level scaffolding, Cortex, Distal-less, Karyotype, Optix, P supergene, Wing pattern genes, Wnt,
• MeSH
• chromozomy * MeSH
• fylogeneze MeSH
• haploidie MeSH
• karyotyp MeSH
• můry * genetika   MeSH
• syntenie MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 virus, has become a global pandemic. While susceptibility to COVID-19 is subject to several external factors, including hypertension, BMI, and the presence of diabetes, it is also genetically determined to a significant extent. Infectious agents require iron (Fe) for proper functioning. Carriers of mutations resulting in increased iron concentrations are understood to be at increased risk of COVID-19. METHODS: We examined HFE genotypes associated with hereditary haemochromatosis (rs1800562 and rs1799945 SNPs) in 617 COVID-19 patients (166 asymptomatic, 246 symptomatic and 205 hospitalised survivors) and 2 559 population-based controls. RESULTS: We found a higher frequency of the minor allele (Tyr282) of the rs1800562 polymorphism (P < 0.002) in patients compared to controls (8.5 % vs 5.5 %). Non-carriers of the minor allele were protected against SARS-Cov-2 infection (OR, 95 %CI; 0.59, 0.42-0.82). The frequency of minor allele carriers was almost identical across asymptomatic, symptomatic, and hospitalised survivors. The rs1799945 variant did not affect disease severity and its occurrence was almost identical in patients and controls (P between 0.58 and 0.84). CONCLUSIONS: In conclusion, our results indicate that presence of the rs1800562 minor allele, which is associated with hereditary haemochromatosis (thus increased levels of plasma Fe), increases susceptibility to SARS-CoV-2.

• Klíčová slova
• COVID-19, HFE, Iron, Polymorphism, Susceptibility,
• MeSH
• COVID-19 * genetika   MeSH
• hemochromatóza * genetika   epidemiologie   MeSH
• histokompatibilita - antigeny třídy I genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mutace MeSH
• protein hemochromatózy genetika   MeSH
• SARS-CoV-2 MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HFE protein, human MeSH Prohlížeč
• histokompatibilita - antigeny třídy I MeSH
• protein hemochromatózy MeSH
• železo MeSH