Loading...
8 results
Search Results
Now showing 1 - 8 of 8
- Influence of the TAS2R38 gene single nucleotide polymorphisms in metabolism and anthropometry in thyroid dysfunctionPublication . Mendes Costa, Marta; Silva, Alda Pereira da; Santos, Ana Carolina; Ferreira, Joana; Mascarenhas, Mário Rui; Bicho, Manuel; Barbosa, AnaThe 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.
- Interaction between HFE and haptoglobin polymorphisms and its relation with plasma glutathione levels in obese childrenPublication . Aguiar, Laura; Marinho, Cláudia; Martins, Rute; Alho, Irina; Ferreira, Joana; Levy, Pilar Quinhones; Faustino, Paula; Bicho, Manuel; Inácio, AngelaObesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress. In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin - and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in childhood obesity.
- ABCA1 polymorphism R1587K in chronic hepatitis C Is gender-specific and modulates liver disease severity through its influence on cholesterol metabolism and liver function: a preliminary studyPublication . Ferreira, Joana; Bicho, Manuel; Serejo, FátimaChronic hepatitis C (CHC) progression is highly variable and can be influenced by lipid metabolism. The ATP-binding cassette transporter A1 (ABCA1) is involved in lipid metabolism and mediates cholesterol efflux from liver cells. ABCA1 gene polymorphism rs2230808 (R1587K) modulates lipid levels as it is located in an ABCA1 protein domain, which is essential for cholesterol efflux. We aimed to analyze the role of ABCA1 polymorphism R1587K (rs2230808) in modulating the biochemical parameters of lipid metabolism and liver function and its association with liver disease severity, according to gender. A total of 161 CHC patients were clinically, histologically, and biochemically evaluated. Genotyping was performed by melting-curve analysis and statistical analysis by SPSS 24.0. There were significant differences between ABCA1_rs2230808 genotypes and total cholesterol, γGT (γ-glutamyl-transpeptidase), and HCV-RNA. Gender differences: in females, ABCA1_rs2230808 (GG or GA) was associated with higher HCV-RNA serum levels; in males, ABCA1_rs2230808 (GG or GA) was associated with higher γGT, lower total cholesterol, increased risk for γGT ≥ 38 UI/L, and total cholesterol < 4.92 mmol/L. Only in the case of males were higher γGT and lower total cholesterol associated with severe fibrosis and steatosis. Total cholesterol < 4.92 mmol/L also associates with severe necroinflammation. We conclude that ABCA1_rs2230808 is gender-specific. ABCA1_rs2230808 Allele G was associated with different clinical and biochemical parameters, which are related to more severe liver disease.
- Role of inflammatory/immune response and cytokine polymorphisms in the severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAS) treatmentPublication . Ferreira, Joana; Oliveira, Mariana; Bicho, Manuel; Serejo, FátimaHost regulatory immune response is involved in the hepatic inflammatory process caused by the hepatitis C virus (HCV). We aimed to determine if HCV clearance with direct-acting antivirals (DAAs) changes the hepatic fibrosis stage, biochemical parameters of liver injury, and inflammatory/immune responses. Sample: 329 chronic hepatitis C (CHC) patients, 134 of them treated with DAAs. Liver fibrosis was evaluated by transient elastography (FibroScan), biochemical and cellular parameters were determined by standard methods, cytokine concentration by enzyme-linked immunoabsorbent assay (ELISA), and genetic polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or endpoint genotyping. Before DAA treatment, severe fibrosis or cirrhosis (F3/4) was associated with higher values of tumor necrosis factor-alpha (TNF-α) and genotypes transforming growth factor-beta-509 C/T_CC (TGF-β-509 C/T_CC), interleukine-10-1082 T/C_CC (IL-10-1082 T/C_CC), and IL-10-592 G/T_GT. After DAA treatment, fewer F3/4 patients and lower values of TNF-α were found. Patients with TNF-α-308 G/A_GG and IL-10-592 G/T_GT were at risk for F3/4. Lack of improvement of liver fibrosis was associated with lower baseline values of platelet count for genotypes TNF-α-308 G/A_GG and haplotype TT/GG of IL-10-1082 T/C and IL-10-592 G/T. Our study showed decreased liver fibrosis/inflammation and normalization of liver injury biomarkers after DAA treatment. It also points to the importance of suppressing the pro-inflammatory response by DAAs in the resolution of hepatitis C, contributing to the improvement of liver damage evaluated by transient elastography.
- Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CβS, MTHFR, NOS3, CYBA, and ACE1Publication . Inácio, Angela; Aguiar, Laura; Rodrigues, Beatriz; Pires, Patrícia; Ferreira, Joana; Bilhim, Tiago; Pisco, João; Bicho, Manuel; Bicho, Maria ClaraObjective: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CβS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. Methods: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher's exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. Results: Results revealed that CβS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CβS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]). Conclusions: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.
- Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter studyPublication . Fevereiro-Martins, Mariza; Santos, Ana Carolina; Marques-Neves, Carlos; Guimarães, Hercília; Bicho, Manuel; Afonso, Conceição; Ferreira, Joana; Santo, Rita Espírito; Jorge Teixeira, Filipa; Rosa, Rita; Carneiro, Cristina Vaz; Ferreira, Marta; Matos, Teresa; Neiva, Luísa; Pereira, Sandra; Aires, Sofia; Parreira, Ricardo; Melnik, Zuzana; Faria, João; Teixeira, Joana; Barros, Pedro; Almeida, Juliana; Malheiro, Bruna; Rodrigues, Patrícia Cunha; Albuquerque, Luís; Freitas, Alice; Kotchekova, Nadezda; Freitas, Rui; Silveira, Ana Cristina; Ferreira, Ana; Morais, Benvinda; Teixeira, Susana; Mota, Mafalda; Guerra, Maria; Coimbra, Lúcia; Gigante, João; Ferreira, Muriel; Lapa, Patrícia; Monteiro, Madalena; Alfaiate, Mário; Rodrigues, Teresa; Pina, Teresa; Rosário, Marta; Silva, Renato; Breda, Jorge; Bazenga, Filipa; Pinto, João AntónioPurpose: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). Methods: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. Results: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. Conclusion: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.
- Genetic modulation of HPV infection and cervical lesions: role of oxidative stress-related genesPublication . Inácio, Angela; Aguiar, Laura; Rodrigues, Beatriz; Pires, Patrícia; Ferreira, Joana; Matos, Andreia; Mendonça, Inês; Rosa, Raquel; Bicho, Manuel; Medeiros, Rui; Bicho, Maria ClaraHuman papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CβS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.
- Towards a global perspective of environmental health : defining the research grounds of an institute of environmental healthPublication . Virgolino, Ana; Antunes, Francisco; Santos, Osvaldo; Costa, Andreia; Matos, Margarida Gaspar de; Bárbara, Cristina; Bicho, Manuel; Caneiras, Catia; Sabino, Raquel Filipa Pinheiro; Nuncio, Maria Sofia; Matos, Olga; Santos, Ricardo; Costa, Joana; Alarcão, Violeta; Gaspar, Tania; Ferreira, Joana; Carneiro, António VazEnvironmental health is at the intersection between health and the environment. However, it still has a recent (and narrow) history as a scientific area, mainly addressing human biomonitoring and toxicological issues. Only recently additional environmental ‘layers’, other than the traditional chemical, biological and physical environmental determinants, have been considered. This broader perspective of environmental health also encompasses digital, psychosocial, political, socioeconomic and cultural determinants, all of them relevant when considering human health from a planetary health paradigm. This reflects the progressive adoption of a systemic perspective regarding the impact of gains for human health and well-being towards a sustainable environment. It also implies a multi-method and participatory approach to understand the intertwined relationship between environmental changes and human health. In this paper, the broader approach to environmental health is discussed in order to ‘set the stage’ for introducing the Institute of Environmental Health (ISAMB) of the Lisbon School of Medicine, Portugal. Each of the research groups and labs that compose ISAMB are presented, as well as their main lines of research. Present and planned contributions of ISAMB to advance knowledge on environmental health and for promoting human health gains in an environmentally sustainable way are also discussed.