Browsing by Author "Martins, M.C."
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- Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope ProjectPublication . Schiele, F.; De Bacquer, D.; Vincent-Viry, M.; Beisiegel, U.; Ehnholm, C.; Evans, A.; Kafatos, A.; Martins, M.C.; Sans, S.; Sass, C.; Visvikis, S.; De Backer, G.; Siest, G.As part of the ApoEurope Project, the apolipoprotein E (apo E) serum concentration and polymorphism were determined in 6934 healthy subjects aged 25-64 years recruited in six European countries: Finland; France; Greece; Northern Ireland; Portugal and Spain. Age and sex influenced apo E concentration with concentrations being significantly higher in men than in women for those aged between 25 and 44 years. The age effect differed between the sexes after the age of 44 years, displaying a linear increase in women and a plateau in men. As expected, the serum apo E concentration was highest in varepsilon2 carriers and lowest in varepsilon4 carriers in each country with a significantly higher frequency of the varepsilon4 allele in the northern regions. The main finding of this study was a clear increasing North-South gradient in serum apo E concentration independent of age, sex and apo E genotype. In subjects aged <45 years and with the varepsilon3/varepsilon3 genotype, apo E concentration was higher in the South-East (Greece) as compared to the North by 20% for men and 32% for women. In addition to the genetic polymorphism, the geographical area is an important factor to take into account when studying serum apo E concentration in multicentre studies and defining reference values.
- Association of gamma glutamyltransferase, metabolic syndrome and cardiovascular riskPublication . Martins, M.C.; Faleiro, L.L.; Afonso, B.; Fonseca, A.Serum gamma-glutamyl transferase (GGT) has been used as a marker of alcohol induced liver disease. Recent epidemiology and pathology studies have suggested its independent role in the pathogenesis and clinical evolution of cardiovascular diseases (CVD) promoting atherosclerosis through an oxidative process leading, within the atherosclerotic plaque, to LDL oxidation, metalloproteinase activation, cell proliferation and apoptosis. Besides it is known that GGT levels rise even in the normal range, with obesity and hepatic steatosis occurs, it is thought, which originates insulin resistance (IR). Being sure that IR is important in the development of type 2 diabetes and CVD, both very prevalent in Portugal, the authors considered as relevant to study the association of GGT with markers of multiple metabolic derangements: insulin-resistance (hyperinsulinemia, hyperglicemia, IR-HOMA = 3), obesity and dyslipidemia. So, a Portuguese sample population, consisted of 123 subjects (52 male and 71 female) was organized. As results were observed: elevation of GGT serum levels with the increasing risk of every marker and the same happened with metabolic syndrome and its components; compared with non obese the group of obese subjects exhibited elevated prevalence of risk factors, though in non obese subjects the percentages of insulin-resistance and dyslipidemias were high (hypercholesterolemia in both sexes, hypertriglyceridemia and low concentrations of HDL-c in men); association of serum GGT levels with every risk factor and metabolic syndrome. Though, as the association with the insulin-resistance state was particularly strong, it is thought that a high prevalence of non-alcoholic fatty liver disease (NAFLD) was present in the studied population. As serum determination of GGT activity is a low-cost, highly sensitive, accurate and frequently used laboratory test and there is association of this enzyme with the most important risk factors of diabetes type 2 and CVD, its serum levels should be considered as a marker of insulin-resistance when NAFLD is supposed to be present or there is obesity.
- Glucose-6-phosphate dehydrogenase deficiency in Portugal: biochemical and mutational profiles, heterogeneity, and haplotype associationPublication . Rodrigues, M.O.; Freire, A.P.; Martins, G.; Pereira, J.; Martins, M.C.; Monteiro, C.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. This deficiency in erythrocytes has a prevalence of 0.51 +/- 0.109 in the Caucasoid male population of Portugal. The frequency for deficiency-conferring genes is 0.39% in the Portuguese population. In the herein study populations males from areas of Portugal presenting with the highest prevalence of G6PD deficiency (Castelo Branco, Setúbal, Faro, and Lisbon) as well as similar subjects located in the border Center/North area of the country (Viseu) have been analyzed for biochemical parameters and screened for mutations and haplotype-associated mutations commensurate with G6PD deficiency. Six intragenic restriction fragment length polymorphisms (RFLPs) were studied: exon 5, nt 376 A -->G, FokI; intron 5, nt 611 C--> G, PvuII; intron 8, nt 163 C--> T, BspHI; exon 10, nt 116 G --> A, PstI; exon 11, nt 1311 C--> T, BclI; and intron 11, nt 93 T -->C, NlaIII. New haplotypes were constructed with the inclusion of intron 11, nt 93 T--> C, NlaIII, and only 5 of 64 possible haplotypes were found to show a marked linkage disequilibrium for several RFLPs and also for mutations and specific haplotypes. The control population (n = 168 males) presented the G6PD B variant and corresponded to haplotypes I (- - + + - -), Ia (- - + + - +), and VIIa (- - + + + +), in 91.8, 2.3, and 5.9%, respectively. The PCR and sequencing analysis of extracted DNAs from the deficient G6PD group showed 48.6% (16/33) of individuals with the G6PD A- mutation, corresponding to haplotype VIa (+ + - + - +); 9% (3/33) with the Betica mutation and 18% (6/33) with the Santa Maria mutation, both of them associated with haplotype IVa (+ - - + \- +); 6.1% (2/33) with the Mediterranean mutation associated with haplotype VIIa; 12.3% (4/33) with the Seattle mutation, 3.0% (1/33) with Gaohe mutation; and a new mutation, 3.0% (1/33), which we designated by G6PD Flores, all of them associated with haplotype I.
- Hereditary anaemias in Portugal: epidemiology, public health significance, and controlPublication . Martins, M.C.; Olim, G.; Melo, J.; Magalhães, H.A.; Rodrigues, M.O.A countrywide prospective study aimed at establishing the prevalence of the haemoglobinopathy genes in the Portuguese population was carried out by screening 15,208 randomly selected blood samples from young males. This male based survey provided the opportunity of assessing simultaneously the prevalence of the red cell enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency, thus giving a picture of these important hereditary anaemias in Portugal. The results showed a low average frequency of beta thalassaemia (0.45%) and haemoglobin S (0.32%) carriers as well as G6PD deficiency (0.51%). However, these disorders are unevenly distributed throughout the country with a higher prevalence in some areas, mainly in the south. The relationship of this pattern of haemoglobinopathies to the known haplotypes linked to beta thalassaemia and sickle cell disease, relevant historical events, and local selective pressure was investigated. Hb D and Hb J are the commonest other structural variants. The implemented programme for control of these hereditary anaemias is described.
- Novel point mutation in exon 12 of the glucose-6- phosphate dehydrogenase gene: G6PD FLORESPublication . Rodrigues, M.O.; Pereira, J.D.; Gaspar, G.; Olim, G.; Martins, M.C.; Monteiro, C.In Portugal there are a wide variety of G6PD deficiency associated mutations. In an individual from the island of Flores of the Azorean archipelago, we report a new mutation in the G6PD gene that gives rise to a "moderate rate of G6PD deficiency" (12.6% of the normal activity) according to WHO criteria. Direct sequencing revealed a C-->A point mutation at position 1387 with the consequent substitution of an Argine by Serine. We designated this new mutation as G6PD FLORES. The mutation is associated with haplotype I ( - - + + - - ), using six intragenic RFLPs. This information may also be seen as contributing to the clarification of the genetic makeup of the Azorean population, founder mutations, and/or gene flow.
- Relação entre a leptina, a massa corporal e a síndrome metabólica numa amostra da população adultaPublication . Martins, M.C.; Lima Faleiro, L.; Fonseca, A.Objetivo Estudar a relação que a leptina tem com a obesidade (expressa em índice de massa corporal) e alguns componentes da síndrome metabólica (SM) numa amostra da população adulta. População e métodos Em 103 indivíduos, 42 homens e 61 mulheres, com idades superiores a 30 anos, clinicamente definidos como não diabéticos mas com patologia cardiovascular e/ou antecedentes familiares de doenças cardiovasculares (DCV), determinaram-se, além da leptina, a insulina, a glicemia em jejum e após ingestão de 75g de glicose, HDL-c, triglicéridos e calcularam-se os índices de resistência à insulina (IR-HOMA) e de massa corporal (IMC). Resultados O IMC, tomado como índice de obesidade geral, condicionou os níveis séricos da leptina. O IMC subiu, em ambos os sexos, à medida que os níveis séricos da leptina se elevaram do 1.° para o 3.° tercil da respetiva distribuição. Foi muito forte a correlação leptina/IMC com r=0,524 nos homens e r=0,603 nas mulheres, significância estatística elevada. Na previsão da hiperleptinemia, a posição cimeira foi assumida pelo IMC com AUC (area under curve) de 0,81 nos homens e 0,84 nas mulheres. Ao avaliar-se a magnitude da associação da leptina aos diferentes fatores de risco (regressão logística binária univariada) observaram-se valores muito altos de odds ratio (OR) para a relação leptina/IMC, em ambos os sexos (10,11 nos homens e 6,00 nas mulheres).Verificou-se mesmo (regressão logística multivariada) que a hiperleptinemia foi condicionada, em ambos os sexos, pela obesidade com OR de 9,30 nos homens e 8,1 nas mulheres, considerando IMC ≥ 30 kg/m2. - A hiperinsulinemia e a IR influenciaram profundamente a hiperleptinemia. Na previsão da IR, a leptina surgiu, em ambos os sexos, como primeiro elemento (AUC=0,89 nos homens e 0,85 nas mulheres) e, na previsão da hiperleptinemia, vêm logo a seguir à obesidade (IMC), a IR nos homens e a hiperinsulinémia nas mulheres com AUC respetivamente de 0,79 e 0,78. Foram fortes as correlações leptina/IR-HOMA e leptina/insulina, em ambos os sexos e enorme a influência que nos homens teve a hiperinsulinémia (OR=11,71) e a IR nas mulheres (OR=21,22). - Relativamente aos componentes da SM: Observou-se elevação dos respetivos níveis séricos, à medida que as concentrações da leptina subiram do 1.° para o 3.° tercil da respetiva distribuição (com exceção do HDL-c, que desceu). Conclusão O aumento da leptina sérica, sobretudo nos indivíduos obesos, deve constituir sinal de alerta para desiquilíbrios energéticos e do regimen alimentar, para a existência de hiperinsulinemia, de IR, de alterações em outros fatores de risco metabólicos que têm profunda influência nas DCV e diabetes tipo 2.