👤 Markus T Juonala

To evaluate the presence of serum protein biomarkers associated with the early phases of formation of carotid atherosclerotic plaques, label-free quantitative proteomics analyses were made for serum samples collected as part of The Cardiovascular Risk in Young Finns Study. Samples from subjects who had an asymptomatic carotid artery plaque detected by ultrasound examination (N = 43, Age = 30-45 years) were compared with plaque free controls (N = 43) (matched for age, sex, body weight and systolic blood pressure). Seven proteins (p < 0.05) that have been previously linked with atherosclerotic phenotypes were differentially abundant. Fibulin 1 proteoform C (FBLN1C), Beta-ala-his-dipeptidase (CNDP1), Cadherin-13 (CDH13), Gelsolin (GSN) and 72 kDa type IV collagenase (MMP2) were less abundant in cases, whereas Apolipoproteins C-III (APOC3) and apolipoprotein E (APOE) were more abundant. Using machine learning analysis, a biomarker panel of FBLN1C, APOE and CDH13 was identified, which classified cases from controls with an area under receiver-operating characteristic curve (AUROC) value of 0.79. Furthermore, using selected reaction monitoring mass spectrometry (SRM-MS) the decreased abundance of FBLN1C was verified. In relation to previous associations of FBLN1C with atherosclerotic lesions, the observation could reflect its involvement in the initiation of the plaque formation, or represent a particular risk phenotype. Show less

Obesity is a known risk factor for cardiovascular disease. Early prediction of obesity is essential for prevention. The aim of this study is to assess the use of childhood clinical factors and the genetic risk factors in predicting adulthood obesity using machine learning methods. A total of 2262 participants from the Cardiovascular Risk in YFS (Young Finns Study) were followed up from childhood (age 3-18 years) to adulthood for 31 years. The data were divided into training (n=1625) and validation (n=637) set. The effect of known genetic risk factors (97 single-nucleotide polymorphisms) was investigated as a weighted genetic risk score of all 97 single-nucleotide polymorphisms (WGRS97) or a subset of 19 most significant single-nucleotide polymorphisms (WGRS19) using boosting machine learning technique. WGRS97 and WGRS19 were validated using external data (n=369) from BHS (Bogalusa Heart Study). WGRS19 improved the accuracy of predicting adulthood obesity in training (area under the curve [AUC=0.787 versus AUC=0.744, WGRS19 improves prediction of adulthood obesity. Predictive accuracy is highest among young children (3-6 years), whereas among older children (9-18 years) the risk can be identified using childhood clinical factors. The model is helpful in screening children with high risk of developing obesity. Show less

The present study was designed to investigate the effects of apoB XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow-mediated vasodilatation (FMD). As part of the Cardiovascular Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265 subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and genotyping of the apolipoprotein polymorphisms was performed. The frequencies of the genotypes did not differ between the groups with high (above median 0.57 mm) and low (below median) IMT, CAC or FMD. The average carotid IMT differed between the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and carotid IMT was not significant in any of the covariate-adjusted logistic and linear regression analyses. CAC and FMD were not influenced by either of the polymorphisms in ANOVA and regression analyses. The polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood. Show less

Apolipoprotein A-I/C-III/A-IV (apoA-I/C-III/A-IV) SstI and apolipoprotein B (apoB) XbaI polymorphisms have been shown to affect serum low-density lipoprotein (LDL) cholesterol concentrations in a sample of Finnish children. We studied whether these polymorphism are associated with carotid artery intima-media thickness (IMT), a marker of pre-clinical atherosclerosis, measured in the same subjects during their adulthood. A random sub-sample of 214 individuals from the "Cardiovascular Risk in Young Finns" study, for whom genotypes, cardiovascular risk factor data and carotid artery IMT measured in 2001 were available, were studied. Mean carotid IMT values increased according to the apoA-I/C-III/A-IV SstI genotype groups in the order of S1S1 (0.58+/-0.08 mm), S1S2 (0.61+/-0.08 mm), and S2S2 (0.70+/-0.16 mm, p=0.02, ANOVA). In multiple linear regression analysis after adjusting for age, sex and body mass index the mean IMT thickness among the S2 allele carriers was higher (p=0.02) compared to non-carriers. In logistic regression analysis the frequency of S2 allele carriers was higher among the high IMT group compared to the low IMT group (OR=4.02, CI: 1.68-9.61, p=0.002). No significant association between apoB XbaI polymorphism and carotid IMT was found. However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups (p<0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns. Show less