Autor(es):
Gaio, Vania 
; Nunes, Baltazar ; Fernandes, Aida ; Mendonça, Francisco ; Horta Correia, Filomena ; Beleza, Álvaro ; Gil, Ana Paula ; Bourbon, Mafalda ; Vicente, Astrid ; Matias Dias, Carlos ; Barreto da Silva, Marta
Data: 2013
Identificador Persistente: http://hdl.handle.net/10400.18/2120
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Metabolic Syndrome; CYP2C19 Gene; Genetic Association Study; Continuous MetS Score; Determinantes da Saúde e da Doença; Doenças Cardio e Cérebro-vasculares
Descrição
Metabolic syndrome (MetS) is a cluster of conditions — increased blood pressure, high blood glucose level, excess body fat around the waist and abnormal cholesterol levels — that occur together, increasing the risk of heart disease, stroke and diabetes. In Portugal, the MetS prevalence is estimated to be 27,5% with regional variations, being highest in the Alentejo (30,99%) and lowest in the Algarve (24,42%), constituting a public health problem.
Although for clinical settings, a binary definition of MetS enabling a yes or no diagnosis is useful, it is clear that dichotomizing a continuous outcome variable reduces the statistical power of the MetS association studies. Therefore, the aim of the present study is to identify genetic risk factors involved in MetS etiology, using a continuous MetS score. To achieve our goal, a principal component analysis was performed to compute a score using the six normalized risk factors for MetS (waist circumference, diastolic and systolic blood pressure, glucose, triglycerides and HDL blood levels), with a higher MetS score indicating a less favorable MetS profile. After calculating this score, an association study was performed using 37 SNPs in candidate genes involved in MetS related diseases. A total of 206 subjects, including 119 women and 87 men (mean age: 56,31± 16,37 years, range: 26-91 years) were included in this analysis. We found 4 SNPs significantly associated with higher MetS scores (rs4244285 (CYP2C19), rs279871 (GABRA2), rs1647 (NPY) and rs1142345(TPMT)). P-values are 4,36x10-4, 1,3x10-2, 1,7x10-2 and 9,76x10-3 respectively. After correcting for multiple testing only rs4244285 (CYP2C19) remains significant (p=0,016). In addition, we have performed a multiple regression analysis considering the CYP2C19 genotype as the independent variable, adjusted for age. The resulting model explains 17% of the MetS score variance. After adding the remaining SNP genotypes that do not survive the multiple testing correction, the same model is able to explain 23,1% of the score. Our findings support the evidence of an association between CYP2C19 rs4244285 gene polymorphism and the MetS score, emphasizing the importance of lipid metabolism, thought cytochrome P450 enzymes, in the MetS etiology. However, further studies will be necessary to replicate these findings in different populations as well as functional studies to clarify the role of this variant in the etiology of MetS.
