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- November 19, 2008 |
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"Genetic Prediction of the Metabolic Syndrome: The Botnia Study"Dr. Valeriya Lyssenko (biography)
English - 2005-04-14 - 13 minutes
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Summary :
Background and aims: The metabolic syndrome is a cluster of risk factors associated with cardiovascular morbidity and mortality. However, underlying genetic susceptibility to the metabolic syndrome has not been extensively studied. The aim of the study was to evaluate the role of common variants in candidate genes for their ability to predict the metabolic syndrome in a large prospective study (the Botnia Study).
Subjects and Methods: 2293 non-diabetic individuals, of whom 1937 without the metabolic syndrome at baseline (873 males/1064 females; age 44 plus/minus 14 years; BMI 25 plus/minus 4 kg/m2) participating in the prospective study were genotyped for variants in peroxisome proliferator-activated receptor gamma (PPARg Pro12Ala), Calpain-10 (CAPN10 SNP-43, -44), muscle glycogen synthase (GYS1 XbaI), b1-, b2- and b3-adrenergic receptor (b1-AR Gly389Arg; b2-AR Arg16Gly; b3-AR Trp64Arg) and adiponectin (APM1 SNP276,-2019) genes. The metabolic syndrome was defined using the NCEP ATP III criteria. Cox proportional hazard models were used to study the association of the genetic variants with the onset of the metabolic syndrome.
Results: During a median 6-year follow-up, 267 (14%) individuals developed the metabolic syndrome. The PPARg Pro12Ala (Pro/Pro-genotype) (HR 1.5, 95% CI 1.1-2.0, P = 0.019) and b1-AR Gly389Arg (Gly-allele) (HR 1.4, 95% CI 1.1-1.8, P = 0.006) variants were associated with increased risk of developing the metabolic syndrome. The multivariate analysis of combined genetic effects revealed an additive effect of the PPARg Pro12Ala and b1-AR Gly389Arg variants.
Conclusion: We demonstrate in a large prospective study that variants in the PPARg and b1-AR genes in additive way predict the metabolic syndrome.
Learning objectives :
After viewing this presentation, participants will be able to discuss:
• The risk of developing the metabolic syndrome in the BOTNIA population
• Which mutations were associated with the development of the metabolic syndrome
• Which components of the metabolic syndrome (ATP-III) were predictable by the mutations studied
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