Loading...
Publication
Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 116.42 KB | Adobe PDF |
Advisor(s)
Abstract(s)
Introdução: Estudos recentes de associação
genómica em larga escala (GWAS)
identificaram vários polimorfismos de um
único nucleótido (SNP), localizados no locus
9p21, associados com doença arterial
coronária (DAC). De entre eles o SNP
rs1333049 demonstrou uma associação
consistente com a DAC tendo sido
reproduzida, com sucesso,
em várias populações.
Objectivo: Investigar se a nova variante
rs1333049, no cromossoma 9p21,
é um factor de risco independente
para DAC, na população Portuguesa.
Material e métodos: Estudo caso-controlo,
que incluiu 1406 indivíduos, 723 doentes
coronários internados consecutivamente
(idade média de 53,7±8,9 anos 79,9% do
sexo masculino) e 683 controlos
sem doença coronária (idade média
de 53,3±10,5 anos, 73,9 % do sexo
masculino) seleccionados para não serem
significativamente diferentes quanto ao sexo
e idade. Estudou-se o SNP rs1333049,
em todos os indivíduos,
com recurso à técnica convencionada de
PCR combinada com a técnica TaqMan (Applied Biosystems). Determinou-se a
distribuição alélica e genotípica (C/G), odds
ratio e respectivo intervalo de confiança
para risco de DAC.
Foi construído um modelo de regressão
logística forward wald ajustado para a
idade, sexo, factores de risco convencionais,
marcadores bioquímicos e genótipos em
estudo, afim de avaliar quais as variáveis
associadas de forma significativa e
independente com DAC.
Resultados: 60% dos doentes coronários e
53% dos controlos apresentaram o alelo C
(OR=1,33; p=0,0002), 35,7% dos doentes e
29,3% dos controlos tinham o genótipo
homozigoto CC (OR=1,34;p=0,010).
O heterozigoto CG estava presente em
48,1% dos doentes e 47% nos controlos,
não atingindo significância estatística, para
risco vascular (OR=1,05;p=0,670). Após
análise multivariada de regressão logística o
genótipo CC do cromossoma 9p21 ficou na
equação com um OR=1,7, p=0,018 e o
genótipo heterozigoto
CG com um OR=1,5, p=0,048.
Conclusão: Com o presente trabalho
replicou-se, numa população portuguesa, o
risco coronário ligado à nova variante
rs1333049 do cromossoma 9p21.
A robustez deste genótipo,
tanto em homo como em heterozigotia,
tem sido consistente e relevante na
estratificação de risco para a DAC,
mesmo em contextos populacionais
muito diversos. Nestas circunstâncias,
a utilização do genótipo CC ou CG
poderá vir a revelar-se útil
para a previsão do risco de DAC
na nossa população.
INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.
INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.
Description
Keywords
Factores de risco Polimorfismos genéticos Doença arterial coronária Locus 9p21 Risk factors Genetic polymorphisms Coronary artery disease Portugal Madeira
Citation
Mendonça, I., Reis, R. P., & Pereira, A. (2011). Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa. Rev Port Cardiol, 30(6), 575-91.