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Background  Metabolic syndrome (MetS) is a cluster of conditions that occur together, increasing the risk of heart disease, stroke and diabetes. Since pathways implicated in different diseases reveal surprising insights into shared genetic bases underlying apparently unrelated traits, we hypothesize that there are common genetic components involved in the clustering of MetS traits. With the aim of identifying these common genetic components, we have performed a genetic association study by integrating MetS traits in a continuous MetS score.    Methods  A cross-sectional study developed in the context of the Portuguese Component of the European Health Examination Survey (EHES) was used. Data was collected through a detailed questionnaire and physical examination. Blood samples were collected and biochemical analyses were performed. Waist circumference, blood pressure, glucose, triglycerides and high density lipoprotein cholesterol (HDL) levels were used to compute a continuous MetS score, obtained by Principal Component Analysis. A total of 37 single nucleotide polymorphisms (SNPs) were genotyped and individually tested for association with the score, adjusting for confounding variables.    Results  A total of 206 individuals were studied. Calculated MetS score increased progressively with increasing number of risk factors ( P  < 0.001). We found a significant association between  CYP2C19 rs4244285  and the MetS score not detected using the MetS dichotomic approach. Individuals with the A allelic variant seem to be protected against MetS, displaying a lower MetS score (Mean difference: 0.847; 95%CI: 0.163-1.531;  P  = 0.015), after adjustment for age, gender, smoking status, excessive alcohol consumption and physical inactivity. An additive genetic effect of  GABRA2 rs279871 ,  NPY rs16147  and  TPMT rs1142345  in the MetS score variation was also found.    Conclusions  This is the first report of a genetic association study using a continuous MetS score. The significant association found between the  CYP2C19  polymorphism and the MetS score but not with the individual associated traits, emphasizes the importance of lipid metabolism in a MetS common etiological pathway and consequently on the clustering of different cardiovascular risk factors. Despite the sample size limitation of our study, this strategy can be useful to find genetic factors involved in the etiology of other disorders that are defined in a dichotomized way.

diabetology and metabolic syndrome

Genetic variation at the CYP2C19 gene associated with metabolic syndrome susceptibility in a South Portuguese population: results from the pilot study of the European Health Examination Survey in Portugal