Contribution of HFE and HPSE genes and methaemoglobin reductase activity to heart failure

Introduction: Heart failure can be defined as a syndrome caused by a structural anomaly and/or by a committed cardiac function, which leads to an inadequate cardiac output unable to meet the metabolic necessities of the organism. We aim to understand if HFE and HPSE genes as well as methaemoglobin reductase activity, may influence the development of heart failure. Methodology: It was performed a case-control study, in which 252 DNA samples from Portuguese individuals were analysed, 143 derived from subjects with heart failure, and 109 from healthy controls. For HPSE genotyping (rs4693608), we performed endpoint PCR analysis. A multiplex ARMS (Amplification-Refractory Mutation System) assay was used for the simultaneous detection of two HFE polymorphisms (C282Y and H63D). Reductase methaemoglobin activity was determined by spectrophotometric methods. All statistical tests were performed with IBM® SPSS® Statistics 26.0 software. Statistical significance was defined as a p-value < 0.05. Results: Regarding the H63D polymorphism, results show the CG genotype as a risk factor [OR (95% CI) = 2.889 (1.041-8.018); p=0.042]. In what concerns HPSE gene, the GG genotype was found to have a protective effect [OR (95% CI) = 0.435 (0.193-0.982); p=0.045] while the presence of the A allele is a risk factor [OR (95% CI) = 2.297 (1.018-5.179); p=0.045. Considering methaemoglobin reductase, its activity was lower in patients than in healthy controls (p=0.019). Discussion: Intravenous iron supplementation is sometimes considered in heart failure treatment, emphasizing the results presented in the present study. Considering the high prevalence of heart failure in Portugal (400.000 individuals, according to Sociedade Portuguesa de Cardiologia), it is important to identify iron-related markers, since it may allow an earlier and more expert approach, which may provide better prevention and therapeutic strategies for this pathology.N/

Study of the interaction between modulators of iron homeostasis and the ACE gene in heart failure

Introduction: Heart failure (HF) refers to a clinical syndrome composed of a set of symptoms and/or signs that originate from a structural and/or functional cardiac anomaly and that give rise to the inability to pump blood in sufficient quantity, to meet the body's metabolic needs. In the present work, we intend to understand how the interaction between the I/D variation in the ACE gene and possible modulators of iron (Fe) homeostasis influence HF. The modulators under study were: the methemoglobin reductase activity, the Hfe gene and heparanase genes (HPSE) Methodology: A case-control study was carried out with 252 Portuguese people, 143 with HF and 109 healthy controls. To analyze the polymorphism in the HPSE gene (rs4693608) endpoint genotyping (LightCycler480) was performed. To analyze both polymorphisms in the Hfe gene (H63D and C282Y), ARMS Multiplex technique was used. For the analysis of the polymorphism in the ECA gene (rs4646994 - I/D) a regular PCR was performed. Methaemoglobin reductase activity was obtained using spectrophotometric assay. All necessary statistical tests were performed using the IBM® SPSS® Statistics 26.0 software, with values considered significant for p < 0.05. Results: There was an association between HF and: 1) the presence of the D allele of the HFe gene (HH vs HD; p=0.049); 2) the presence of the A allele of the HPSE gene (AA + GA vs GG; p=0.045; 3) lower levels of methemoglobin reductase activity (p=0.019). It was also found that epistasis between the presence of the H or C allele of the Hfe gene and the D allele of the ACE gene are protective in HF (p=0.041 for both). Conclusion: Results of this study highlight the role of iron homeostasis and its interaction with ACE in HF. Iron is an essential component for the proper functioning of mitochondria, which play an important role in providing energy to the heart muscle. Knowledge of the genotype profile of patients, in modulating genes of iron homeostasis in interaction with the ACE gene could be an advantage in the application of a more personalized medicine, allowing preventive counseling and more targeted therapy.info:eu-repo/semantics/publishedVersio

Influence of the TAS2R38 gene single nucleotide polymorphisms in metabolism and anthropometry in thyroid dysfunction

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline–alanine–valine) and non-bitter-tasting by AVI (alanine–valine–isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass—kg, lean mass—kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia—mg/dL, insulinemia—µIU/mL, HOMA-IR, uricemia—mg/dL, calcemia—mg/dL and BMI—kg/m2); ELISA (leptinemia—ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity—UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine–valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726–4.676]), p < 0.001/OR = 8.915; IC95% [4.286–18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine–valine (OR = 0.467; IC95% [0.289–0.757], p = 0.002/OR = 0.132; IC95% [0.056–0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282–0.737], p = 0.001/OR = 0.101; IC95% [0.041–0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine–isoleucine), lean-mass (P49A-proline–proline; PVI), leptin (AVI), HbA1c (A262V-alanine–valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine–alanine), HbA1c (PVV), uricemia (V296I-valine–isoleucine), glycemia (A262V-alanine–alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine–valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine–valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.The writing of the manuscript was also supported by funds from the Foundation for Science and Technology to ISAMB (ref. UIDB/04295/2020 and UIDP/04295/2020).info:eu-repo/semantics/publishedVersio

May the polymorphisms of iron metabolism modulate metabolic and bone remodelling parameters associated with osteoporosis?

Introduction:- Osteoporosis is a multifactorial disease whose interaction between genetic and environmental factors lead to a reduction of bone mineral density accompanied by changes in bone microarchitecture level, leading to a significant decrease in bone strength and an increased fracture risk. - Iron is known to play a relevant role in the development of osteoporosis as it suppresses osteoblast formation and may also stimulate osteoclast resorption of bone. As so, polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis. - HFE is a major histocompatibility complex class I-like protein which gene is commonly mutated in Hereditary Hemochromatosis, a disorder characterized by excessive intestinal iron absorption and its deposition in several organs. It has been postulated that HFE may contribute to iron metabolism regulation by activating hepcidin synthesis in hepatocytes and regulating the expression of iron metabolism-related genes (ferroportin) in duodenum and other cells. - The locus encoding HFE is located on the long arm of chromosome 6 (6q22.2) and contains 2 major polymorphisms. A 845G-A transition resulting in a cys282-to-tyr (C282Y) substitution and a C-to-G transversion in exon 2 resulting in a his63-to-asp substitution (H63D). - Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity. - The locus encoding haptoglobin is located on the long arm of chromosome 16 (16q22.2) and presents a copy number variation polymorphism (CNV) that results from an internal duplication of a gene segment (exons 3 and 4). This gives rise to three different genotypes (Hp1.1, Hp 2.1 and Hp2.2) that modulate the half-life of Hp-Hb complex, its plasma concentration as well as other functions (angiogenesis, immune, etc

Estudo da interação entre moduladores da homeostasia do ferro e o gene ECA na insuficiência cardíaca

Introdução: A insuficiência cardíaca (IC) diz respeito a um síndrome clínico composto por um conjunto de sintomas e/ou sinais com origem numa anomalia cardíaca estrutural e/ou funcional e que dá origem à inabilidade de bombear sangue em quantidade suficiente, de forma a preencher as necessidades metabólicas do organismo. No presente trabalho, pretendemos perceber como a interação entre a variação I/D no gene ECA e possíveis moduladores da homeostasia do ferro (Fe) influenciam a IC. Os moduladores em estudo foram: a atividade da redutase da metahemoglobina, o gene Hfe e o gene da heparanase (HPSE) Metodologia: Foi efetuado um estudo de caso-controlo, no qual foram utilizadas 252 amostras de portugueses, 143 indivíduos com IC e 109 controlos saudáveis. Para analisar o polimorfismo no gene HPSE (rs4693608) foi feita a genotipagem por endpoint (LightCycler480). Para analisar os polimorfismos no gene Hfe (H63D e C282Y) recorreu-se à técnica de ARMS Multiplex. Para a análise do polimorfismo no gene ECA (rs4646994 - I/D) realizou-se um PCR. A atividade da redutase da metahemoglobina foi obtida por testes espetrofotométricos. Todos os testes estatísticos necessários foram realizados no software IBM® SPSS® Statistics 26.0, tendo os valores sido considerados significativos para um p < 0,05. Resultados: Verificou-se uma associação entre a IC e: 1) a presença do alelo D do gene HFe (HH vs HD; p=0,049); 2) a presença do alelo A do gene HPSE (AA + GA vs GG; p=0,045; 3) níveis mais baixos da atividade da redutase da metahemoglobina (p=0.019). Verificou-se ainda que as epistasias entre a presença do alelo H ou C do gene Hfe e o alelo D do gene ECA são protetores na IC (p=0,041 para ambas). Conclusão: Os resultados deste estudo evidenciam o papel da homeostasia do ferro e da sua interação com a ECA na IC. O ferro é um componente essencial para o bom funcionamento das mitocôndrias, as quais têm um papel importante no fornecimento de energia ao musculo cardíaco. O conhecimento do perfil genótipo dos doentes em genes moduladores da homeostasia do ferro em interação com o gene ECA, poderá ser uma vantagem na aplicação de uma medicina mais personalizada, permitindo um aconselhamento preventivo e uma terapêutica mais dirigidos.info:eu-repo/semantics/publishedVersio

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Letter from the member of Editorial Board Prof. Mário Rui Mascarenhas

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