1,168 research outputs found
A historical cohort study
OK Funding Information: Catarina R. Palma dos Reis acknowledges support from a Clarendon Fund Scholarship. Publisher Copyright: © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).Introduction: The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction. Material and methods: This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week. Results: 125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, β = −3.001, (−3.713 to −2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); β = −0.698 (−1.064 to −0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061–19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06). Conclusions: sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.publishersversionepub_ahead_of_prin
A Preliminary Exploration of the Placental Position Influence on Uterine Electromyography Using Fractional Modelling
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.The uterine electromyogram, also called electrohysterogram (EHG), is the electrical signal generated by uterine contractile activity. The EHG has been considered an expanding technique for pregnancy monitoring and preterm risk evaluation. Data were collected on the abdominal surface. It has been speculated the effect of the placenta location on the characteristics of the EHG. In this work, a preliminary exploration method is proposed using the average spectra of Alvarez waves contractions of subjects with anterior and non-anterior placental position as a basis for the triple-dispersion Cole model that provides a best fit for these two cases. This leads to the uterine impedance estimation for these two study cases. Non-linear least square fitting (NLSF) was applied for this modelling process, which produces electric circuit fractional models’ representations. A triple-dispersion Cole-impedance model was used to obtain the uterine impedance curve in a frequency band between 0.1 and 1 Hz. A proposal for the interpretation relating the model parameters and the placental influence on the myometrial contractile action is provided. This is the first report regarding in silico estimation of the uterine impedance for cases involving anterior or non-anterior placental positions.publishersversionpublishe
Adaptive Filtering for the Maternal Respiration Signal Attenuation in the Uterine Electromyogram
Funding Information: For Arnaldo Batista and Manuel Ortigueira, this work was supported by the Portuguese National Funds, through the FCT Foundation for Science and Technology, within the scope of the CTS Research Unit, Center of Technology and Systems, UNINOVA, under the project UIDB/00066/2020 (FCT). Helena Mouriño was financed by national funds through FCT, Fundação para a Ciência e a Tecnologia, under the project UIDB/00006/2020. Publisher Copyright: © 2022 by the authors.The electrohysterogram (EHG) is the uterine muscle electromyogram recorded at the abdominal surface of pregnant or non-pregnant woman. The maternal respiration electromyographic signal (MR-EMG) is one of the most relevant interferences present in an EHG. Alvarez (Alv) waves are components of the EHG that have been indicated as having the potential for preterm and term birth prediction. The MR-EMG component in the EHG represents an issue, regarding Alv wave application for pregnancy monitoring, for instance, in preterm birth prediction, a subject of great research interest. Therefore, the Alv waves denoising method should be designed to include the interference MR-EMG attenuation, without compromising the original waves. Adaptive filter properties make them suitable for this task. However, selecting the optimal adaptive filter and its parameters is an important task for the success of the filtering operation. In this work, an algorithm is presented for the automatic adaptive filter and parameter selection using synthetic data. The filter selection pool comprised sixteen candidates, from which, the Wiener, recursive least squares (RLS), householder recursive least squares (HRLS), and QR-decomposition recursive least squares (QRD-RLS) were the best performers. The optimized parameters were L = 2 (filter length) for all of them and λ = 1 (forgetting factor) for the last three. The developed optimization algorithm may be of interest to other applications. The optimized filters were applied to real data. The result was the attenuation of the MR-EMG in Alv waves power. For the Wiener filter, power reductions for quartile 1, median, and quartile 3 were found to be −16.74%, −20.32%, and −15.78%, respectively (p-value = 1.31 × 10−12).publishersversionpublishe
Reclassification of the intermediate group classified according to heartscore taking in considertaion individual genetic predisposition to coronary artery disease
PosterIntroduction: Cardiovascular risk stratification has included traditional cardiovascular risk factors (TRF) including tobacco, cholesterol and blood pressure adjusted to age and sex. The utility of genetic risk scores (GRS) as predictors of cardiovascular risk remains inconclusive. Objective: We intended to evaluate the ability of a multilocus
GRS within the intermediate risk subgroup, defined by the European Heart score, to add predictive power for the association with coronary artery arterial disease (CAD).
Methods: After applying European SCORE (ES) stratification to a total population of 2703 Portuguese individuals, 639 individuals with 59.0 ± 4.3 years were considered to be at intermediate risk subgroup (2
Results: GRS was an independent predictor for CAD (OR=2.411; pinfo:eu-repo/semantics/publishedVersio
Genetic polymorphisms and coronary artery disease in the portuguese population: the GENEMACOR Study
PosterMultiple studies have showed an association between genetic polymorphisms and the risk of coronary artery disease (CAD). Initially, studies focused mainly in variants acting in pathophysiological axis of CAD or its risk factors. Genome-Wide Association Studies (GWAS) revealed other genes that, besides having an unknown mechanism, are statistically significant. The importance of these in the development of CAD in the Portuguese population is unknown.
Objective: Analyze the genetic polymorphisms associated with the development of CAD in a Portuguese population.
Methods: We performed a case-control study with 1321 consecutive coronary patients (mean age 53.4 ± 8.1 years, 78.8% male) and 1148 controls (adjusted for age and sex) selected from GENEMACOR Study, an ongoing study designed to analyze the genetic profile of a Portuguese population. We evaluated, in both groups, 29 genetic variants previously associated with CAD: ACE I/D, AGT235 M/T, ATIR A/C, MTHFR C/T and 1298 A/C, PON192 Q/R and 55 L/M,LPA T/C, APO E, Locus 9p21.3 (rs1333049), CDKN2B (rs4977574), GJA4 C/T, PCSK9 A/G, TAS2R50 A/G, KIF6 C/T, IGF2BP2 G/T, ADAMTS7 A/G, MC4R T/C, PPARG Pro12 Ala, ZNF259 C/G, SMAD3 C/T, MIA3 C/A, MTHFD1L A/G, SLC30A8 C/T, TCF7L2 C/T, HNF4 C/G, FTO A/C and ADIPOQ C/G. Allele and genotypic frequencies of individuals with and without CAD were compared and the strength of association was expressed by the OR as well as by CI 95%.
Results: The variants rs4340 (ACE I/D), rs266729 (ADIPOQ C/G), rs458560 (PON55 L/M), rs429358 (APOE2), LPA T/C, rs1333049 (locus 9p21.3) and rs4977574 (CDKN2B A/G) were significantly associated with CAD (p<0.05) (Table).
Conclusions: In our population, the genetic polymorphisms significantly related to CAD were: ACE, associated with hypertension; ADIPOQ, associated with obesity; PON55, associated with oxidation; APOE and LPA, associated with dyslipidemia and finally the locus 9p21.3 with a unclear mechanism so far.info:eu-repo/semantics/publishedVersio
Automatic contraction detection using uterine electromyography
UIDB/00066/2020 UID/MAT/04561/2019 PD/BDE/150312/2019Electrohysterography (EHG) is a promising technique for pregnancy monitoring and preterm risk evaluation. It allows for uterine contraction monitoring as early as the 20th gestational week, and it is a non-invasive technique based on recording the electric signal of the uterine muscle activity from electrodes located in the abdominal surface. In this work, EHG-based contraction detection methodologies are applied using signal envelope features. Automatic contraction detection is an important step for the development of unsupervised pregnancy monitoring systems based on EHG. The exploratory methodologies include wavelet energy, Teager energy, root mean square (RMS), squared RMS, and Hilbert envelope. In this work, two main features were evaluated: contraction detection and its related delineation accuracy. The squared RMS produced the best contraction (97.15 ± 4.66%) and delineation (89.43 ± 8.10%) accuracy and the lowest false positive rate (0.63%). Despite the wavelet energy method having a contraction accuracy (92.28%) below the first-rated method, its standard deviation was the second best (6.66%). The average false positive rate ranged between 0.63% and 4.74%—a remarkably low value.publishersversionpublishe
Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease
Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.info:eu-repo/semantics/publishedVersio
Pulse wave velocity and coronary risk stratification.
Introdução: A compliance arterial ou
distensibilidade é uma determinante
fundamental nas doenças cardiovasculares,
apresentando grande interesse a sua medição
não invasiva. A velocidade da onda de pulso
(VOP) é usada, actualmente, como um índice
de distensibilidade arterial.
Objectivos: Avaliar se a VOP constitui um
factor de risco, independente, para doença
das artérias coronárias (DAC). Investigar se
a determinação da mesma pode constituir
uma ferramenta útil, na estratificação do
risco cardiovascular, tanto nos indivíduos
assintomáticos, como nos doentes com DAC
População e Métodos: 811 indivíduos,
301 consecutivos com DAC, confirmada
por coronário-angiografia, média de idade
53,7±10,0 anos e 510 assintomáticos,
seleccionados das listas eleitorais, média
de idade 46,1±10,0 anos. Os indivíduos
assíntomáticos formavam o grupo A e eram
subdivididos em A1 (grupo sem HTA,
dislipidémia e ou diabetes) e A2 (grupo com
HTA, dislipidémia, e ou diabetes). Os doentes
coronários constituiam o grupo B, também
sub dividido em B1 sem HTA, dislipidémia e
ou diabetes e B2 com HTA, dislipidemia e ou
diabetes. Os dados foram expressos em média
± desvio padrão (DP). O teste t de Student foi
usado para comparar as variáveis contínuas e
o c2 para comparar as variáveis categóricas.
A força da correlação independente entre
as variáveis contínuas foi avaliada segundo
Pearson. Finalmente, foi efectuado um modelo
de regressão logística (step by step) para
avaliar quais as variáveis que se relacionavam de forma significativa e independente com
a DAC. A análise estatística foi efectuada
através do software SPSS for Windows, sendo o
valor de p <0,05 considerado significativo.
Resultados: Comparando os dois grupos,
A1 e A2, no primeiro, a média da VOP foi
significantemente mais baixa em relação ao
A2. Comparando o grupo B1 e B2, também no
grupo B1 a média da VOP é mais baixa. No
grupo A1 a VOP correlacionou-se, segundo
Pearson, com a idade, pressão arterial sistólica
(PAS), diastólica e média, IMC, glicémia,
colesterol total, LDL, relação CT/HDL, ApoB,
triglicerídeos, ingestão de álcool, relação
cintura/anca (C/A), e proteína C reactiva(as).
A correlação foi inversa com o colesterol HDL.
No grupo A2 a correlação da VOP foi positiva
com a idade, PAS, PAM, PAD, glicémia, CT/
HDL e pressão do pulso (PP). No grupo B1
a correlação foi positiva e significante com a
idade, PAS, PAM, PAD e PP. Foi inversa com
a fracção de ejecção do VE. No grupo B2, foi
positiva e significante com a idade, PAS, PAM,
relação C/A, PP e homocisteína.
Conclusão: A VOP foi sempre, quer nos
indivíduos assintomáticos quer nos doentes
coronários, mais elevada nos grupos com
maior número de factores de risco. Esta
constatação sugere influência cumulativa
dos factores de risco, no processo de rigidez
arterial. Correlacionou-se de forma positiva
e significativa, com alguns dos factores de
risco clássicos e alguns dos novos marcadores
bioquímicos de risco. Após análise de
regressão logística, manteve-se na equação de
forma significativa, mostrando ser um factor
de risco independente para DAC. Assim, a
avaliação da distensibilidade arterial, através
da medição da VOP, poderá representar um
método simples, rápido e não invasivo, capaz
de estratificar o risco de DAC, tanto nos
indivíduos assintomáticos com nos doentes
coronários.BACKGROUND:
Arterial compliance or stiffness is an important determinant of cardiovascular disease and there is considerable interest in its noninvasive measurement. Pulse wave velocity (PWV) is widely used as an index of arterial stiffness.
AIM:
To determine whether PWV is useful for risk stratification in both healthy individuals and coronary patients.
METHODS:
Control subjects, n=510, aged 46.1 +/- 11 years, with no history of coronary disease, were selected from electoral rolls, and coronary patients, n=301, aged 53.7 +/- 10 years, were selected from hospital patients with a history of coronary artery disease (CAD) confirmed by coronary angiogram (at least 75% obstruction of one of the main coronary vessels). The asymptomatic subjects without CAD formed Group A, and were subdivided into A1 (without hypertension, dyslipidemia and/or diabetes) and A2 (with hypertension, dyslipidemia and/or diabetes). The coronary patients formed Group B, who were also subdivided into B1, without these classic risk factors, and B2 with hypertension, dyslipidemia and/or diabetes. We used the Student's t test to compare continuous variables and the chi-square test to compare categorical data. The strength of correlation between continuous variables was tested by Pearson's linear correlation. Independent variables predictive of CAD were determined by backward logistic regression analysis. The statistical analysis was performed using SPSS for Windows version 11.0 and data were expressed as means +/- SD; a p value of 0.05 was considered significant.
RESULTS:
Comparing the two groups A1 and A2, mean PWV was significantly lower in group A1. Comparing B1 and B2, mean PWV was also significantly lower in group B1. In group A1, PWV was significantly and positively correlated with age, body mass index, waist-to-hip ratio, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean blood pressure (BP), blood glucose, apo B, triglycerides, and high-sensitivity C-reactive protein, unlike HDL which was inversely correlated (Pearson's coefficient). In group A2, PWV was significantly and positively correlated with age, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean BP, blood glucose and pulse pressure (PP), but not HDL, which was inversely correlated with PWV. In group B1, PWV was only significantly and positively correlated with age, systolic, mean, and diastolic BP and PP, and presented a significant inverse correlation with ejection fraction. However, in the high-risk coronary population (group B2), there was a positive correlation with age, waist-to-hip ratio, systolic and mean BP, PP and homocysteine. After stepwise logistic regression, PWV remained in the model and proved to be a significant and independent risk factor for CAD.
CONCLUSION:
The results of our study show that PWV is higher in high-risk groups and significantly correlated with many classic and new CAD risk markers, suggesting that there is a cumulative influence of risk factors in the development of arterial stiffness. We believe that PWV is a useful index of vascular status and hence cardiovascular risk and that it may be useful for risk stratification in both asymptomatic and coronary patients.info:eu-repo/semantics/publishedVersio
Human Paraoxonase Gene Polymorphisms and Coronary Artery Disease Risk
Introdução: As doenças complexas como a
doença das artérias coronárias (DAC), a
hipertensão e a diabetes, são usualmente
causadas pela susceptibilidade individual a
múltiplos genes, factores ambientais e pela
interacção entre eles. As enzimas da
paraoxonase humana (PON), particularmente a
PON1, têm sido implicadas na patogenia da
aterosclerose e da DAC. Dois polimorfismos
comuns na região codificante do gene, com
substituição Glutamina (Q) /Arginina (R) na
posição 192 e Leucina /Metionina na posição
55 influenciam a actividade da PON1. Vários
estudos têm investigado a associação entre os
polimorfismos da PON1 e a DAC, com
resultados contraditórios.
Objectivo: 1- Avaliar a associação dos
polimorfismos da PON1 com o risco de DAC.
2-Estudar a interacção destes polimorfismos
com outros situados em genes candidatos
diferentes, na susceptibilidade para o
aparecimento da DAC.
Material e Métodos: Estudámos em 298
doentes coronários e 298 controlos saudáveis,
através de um estudo caso/controlo, o risco de
DAC associado aos polimorfismos da PON1,
192Q/R e 55L/M. Numa segunda fase
avaliámos o risco das interacções polimórficas
PON1 192 RR + MTHFR 1298 AA; PON1
192 R/R + ECA DD; PON1 192 R/R + ECA 8
GG. Finalmente construímos um modelo de
regressão logística (no qual entraram todas as
variáveis genéticas, ambientais e bioquímicas,
que tinham mostrado significância estatística
na análise univariada), para determinar quais
as que se relacionavam de forma significativa e
independente com DAC.
Resultados: Verificámos que o genótipo PON155 MM tinha uma distribuição superior na
população doente mas não atingia significância
estatística como factor de risco para DAC. O
PON1 199 RR apresentou um risco relativo
80% superior relativamente à população que o
não possuía (p=0,04). A interacção da PON1
192 RR e da MTHFR 1298 AA, polimorfismos
sedeados em genes diferentes, apresentou um
risco relativo de DAC de 2,76
(OR=2,76;IC=1,20- 6,47; P=0,009), bastante
superior ao risco de cada polimorfismo isolado,
assim como a associação da PON1 RR + ECA
DD (com polimorfismos também sedeados em
genes diferentes), que apresentou um risco
337% superior relativamente aos que não
possuíam esta associação (OR=4,37;IC=1,47-
13,87; P=0,002). Da mesma forma a associação
entre a PON1 RR e ECA 8 GG, revelou um
risco ainda mais elevado (OR=6;23; IC=1,67-
27,37; P<0,001). Após modelo de Regressão
Logística as variáveis que ficaram na equação
representando factores de risco significativos e
independentes para DAC, foram os hábitos
tabágicos, doença familiar, diabetes,
fibrinogénio, Lp (a) e a associação PON1 192
RR + ECA 8 GG. Esta última associação
apresentou, na regressão logística, um
OR=14,113; p=0,018
Conclusões: O genótipo PON1 192 RR
apresentou, se avaliado isoladamente, um risco
relativo de DAC 80% superior relativamente à
população que não possuía este genótipo. A
associação deste polimorfismo com outros
polimorfismos sedeados em genes diferentes,
codificando para diferentes enzimas e
pertencendo a sistemas fisiopatológicos
distintos (MTHFR1298 AA, ECA DD e ECA 8
GG), aumentou sempre o risco de eclosão da
DAC. Após correcção para os outros factores
de risco clássicos e bioquímicos, a associação
PON1 192 RR + ECA 8 GG, continuou a ser
um factor de risco significativo e independente
para CAD.Background: Complex diseases such as
coronary artery disease (CAD), hypertension
and diabetes are usually caused by individual
susceptibility to multiple genes, environmental
factors, and the interaction between them. The
paraoxonase 1 (PON1) enzyme has been
implicated in the pathogenesis of
atherosclerosis and CAD. Two common
polymorphisms in the coding region of the
PON1 gene, which lead to a glutamine
(Q)/arginine (R) substitution at position 192
and a leucine (L)/methionine (M) substitution
at position 55, influence PON1 activity. Studies
have investigated the association between these
polymorphisms and CAD, but with conflicting
results.
Aims: 1) To evaluate the association between
PON1 polymorphisms and CAD risk; and 2) to
study the interaction between PON1
polymorphisms and others in different
candidate genes.
Methods: We evaluated the risk of CAD
associated with PON1 Q192R and L55M
polymorphisms in 298 CAD patients and 298
healthy individuals. We then evaluated the risk
associated with the interaction of the PON1
polymorphisms with ACE DD, ACE 8 GG and
MTHFR 1298AA. Finally, using a logistic
regression model, we evaluated which variables
(genetic, biochemical and environmental) were
linked significantly and independently with
CAD.
Results: We found that the PON1 55MM
genotype was more common in the CAD population, but this did not reach statistical
significance as a risk factor for CAD, while
PON1 192RR presented an 80% higher
relative risk compared to the population
without this polymorphism. The interaction
between PON1 192RR and MTHFR 1298AA,
sited in different genes, increased the risk for
CAD, compared with the polymorphisms in
isolation (OR=2.76; 95% CI=1.20-6.47;
p=0.009), as did the association of PON1
192RR with ACE DD, which presented a
337% higher risk compared to the population
without this polymorphic association
(OR=4.37; 95% CI=1.47-13.87; p=0.002).
Similarly, the association between PON1
192RR and ACE 8 GG was linked to an even
higher risk (OR=6.23; 95% CI=1.67-27.37;
p<0.001). After logistic regression, smoking,
family history, fibrinogen, diabetes, Lp(a) and
the association of PON1 192RR + ACE 8 GG
remained in the regression model and proved
to be significant and independent risk factors
for CAD. In the regression model the latter
association had OR=14.113; p=0.018.
Conclusion: When analyzed separately, the
PON1 192RR genotype presented a relative
risk for CAD 80% higher than in the
population without this genotype. Its
association with other genetic polymorphisms
sited in different genes, coding for different
enzymes and belonging to different
physiological systems, always increased the
risk for CAD. After correction for other
conventional and biochemical risk factors, the
PON1 192RR + ACE 8 GG association
remained a significant and independent risk
factor for CAD.info:eu-repo/semantics/publishedVersio
Gene-Gene Interaction Affects Coronary Artery Disease Risk
Introdução: Existem vários estudos que
comparam doentes coronários e controlos, no
sentido de determinar quais os polimorfismos
que apresentam risco acrescido de doença das
artérias coronárias (DC). Os seus resultados
têm sido muitas vezes contraditórios, mas
apresentam uma limitação suplementar:
avaliam os polimorfismos um a um, quando
na natureza os polimorfismos não existem
isolados. Põe-se a questão se serão mais
importantes associações de polimorfismos
mutados no mesmo gene ou em genes
diferentes.
Objectivo: Com o presente trabalho
pretendemos avaliar o risco da associação de
polimorfismos em termos de aparecimento de
DC no mesmo gene ou em genes diferentes.
Metodologia: Estudámos em 298 doentes
coronários e 298 controlos sãos o risco
associado aos polimorfismos (genótipos
considerados de risco), DD da Enzima de
Converaão da Angiotensina (ECA) I/D; GG da
ECA 8, MM do Angiotensinogénio (AGT) 174;
TT do AGT 235; TT da Metiltetrahidrofolato
Reductase (MTHFR) 677; AA da MTHFR
1298;RR da Paraoxonase1 (PON1) 192 e MM
da PON1 55. Posteriormente avaliámos o risco
ligado às associações no mesmo gene (DD da
ECA + GG da ECA 8; MM do AGT174 + TT
do AGT 235; TT da MTHFR 677 + AA da
MTHFR 1298). Finalmente, nos polimorfismos
que isoladamente apresentavam significância,
avaliámos o risco das associações de
polimorfismos a níveis funcionais diferentes (ECA + AGT; ECA + MTHFR; ECA + PON1.
Finalmente através de um modelo de regressão
logística fomos determinar quais as variáveis
que se relacionavam de forma significativa e
independente com a DC.
Resultados: Os polimorfismos isolados como:
ECA DD [P<0.0001], ECA 8 GG [P=0,023],
e MTHFR 1298 AA [P=0,049]), apresentaram
uma frequência mais elevada nos casos,
associando-se de forma significativa ao grupo
com DC. A associação de polimorfismos no
mesmo gene não teve efeito sinergístico ou
aditivo e não aumentou o risco de DC. A
associação polimórfica em genes diferentes
aumentou o risco de DC quando comparada
com o risco do polimorfismo isolado. No caso
da associação da ECA DD ou ECA 8 GG
com a PON1 192 RR, o risco quadruplicou
(OR passou de 1,8 para 4,2). Após regressão
logística o hábito tabágico, a história familiar,
o fibrinogénio, diabetes, a associação ECA
DD ou ECA 8 GG com a MTHFR 1298 AA
e a interacção ECA DD ou ECA 8 GG com
a PON1 192 RR permaneceram na equação,
mostrando ser factores de risco independente
para DC.
Conclusões: A associação de polimorfismos
mutados no mesmo gene nunca aumentou o
risco do polimorfismo isolado. A associação
com interacção de polimorfismos mutados
em genes diferentes, pertencentes a sistemas
fisiopatológicos e enzimáticos diferentes,
esteve sempre associada a maior risco do
que cada polimorfismo por si. Este trabalho
levanta, pela primeira vez, a possibilidade
de tentativa de compreensão do risco
genético coronário em conjunto e não de cada
polimorfismo por si.Introduction: Various studies have compared
coronary artery disease (CAD) patients
with controls in order to determine which
polymorphisms are associated with a higher
risk of disease. The results have often been
contradictory. Moreover, these studies
evaluated polymorphisms in isolation and not
in association, which is the way they occur in
nature.
Objective: Our purpose was to evaluate the
risk of CAD in patients with associated
polymorphisms in the same gene or in different
genes.
Methods: We evaluated the risk associated
with ACE DD, ACE 8 GG, AGT 174MM, AGT
235TT, MTHFR 677TT, MTHFR 1298AA,
PON1 192RR and PON1 55MM in 298
CAD patients and 298 healthy individuals.
We then evaluated the risk of associated
polymorphisms in the same gene (ACE DD
+ ACE 8 GG; AGT 174MM + AGT 235TT;
MTHFR 677TT + MTHFR 1298AA).
Finally, for the isolated polymorphisms
which were significant, we evaluated the risk
of polymorphism associations at different
functional levels (ACE + AGT; ACE +
MTHFR; ACE + PON1). Multiple logistic
regression was used to identify independent
risk factors for CAD.
Results: Isolated polymorphisms including
ACE DD (p<0.0001), ACE 8 GG (p=0.023), and MTHFR 1298AA (p=0.049) presented
with a significantly higher frequency in the
CAD group. An association of polymorphisms
in the same gene did not have an additive
or synergistic effect, nor did it increase the
risk of CAD. Polymorphic associations in
different genes increased the risk of CAD,
compared with the isolated polymorphisms.
The association of ACE DD or ACE 8 GG
with PON1 192RR increased the risk of CAD
fourfold (1.8 to 4.2). After logistic regression
analysis, current smoking, family history,
fibrinogen, diabetes, and the ACE DD or
ACE 8 GG + MTHFR 1298AA and ACE DD
or ACE 8 GG + PON1 192RR associations
remained in the model and proved to be
independent predictors of CAD.
Conclusions: The association of
polymorphisms in the same gene did not
increase the risk of the isolated polymorphism.
The association of polymorphisms in genes
belonging to different enzyme systems was
always linked to increased risk compared to
the isolated polymorphisms.
This study may contribute to a better
understanding of overall genetic risk for
CAD rather than that associated with each
polymorphism in isolation.info:eu-repo/semantics/publishedVersio
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