The Gene Score for Predicting Hypertriglyceridemia: New Insights from a Czech Case-Control Study
Language English Country New Zealand Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31222479
DOI
10.1007/s40291-019-00412-2
PII: 10.1007/s40291-019-00412-2
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Genetic Predisposition to Disease * MeSH
- Genetic Association Studies * methods MeSH
- Genetic Testing MeSH
- Genotype MeSH
- Hypertriglyceridemia blood diagnosis epidemiology genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Comorbidity MeSH
- Middle Aged MeSH
- Humans MeSH
- Odds Ratio MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
BACKGROUND: Plasma triglyceride (TG) values are significant predictors of cardiovascular and total mortality. The plasma levels of TGs have an important genetic background. We analyzed whether 32 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies are discriminators of hypertriglyceridemia (HTG) in the Czech population. OBJECTIVES: The objective of this study was to replicate and test the original findings in an independent study and to re-analyze the gene score leading to HTG. METHODS: In total, we analyzed 32 SNPs in 209 patients with plasma TG levels over 10 mmol/L (HTG group) and compared them in a case-control design with 524 treatment-naïve controls (normotriglyceridemic [NTG] group) with plasma TG values below 1.8 mmol/L. RESULTS: Sixteen SNPs were significantly associated with an increased risk of HTG development, with odds ratios (ORs) (95% confidence interval [CI]) varying from 1.40 (1.01-1.95) to 4.69 (3.29-6.68) (rs964184 within the APOA5 gene). Both unweighted (sum of the risk alleles) and weighted gene scores (WGS) (log of the achieved ORs per individual genotype) were calculated, and both gene scores were significantly different between groups. The mean score of the risk alleles was significantly increased in the HTG group compared to the NTG group (18.5 ± 2.5 vs. 15.7 ± 2.3, respectively; P < 0.00001). Subjects with a WGS over 9 were significantly more common in the HTG group (44.5%) than in the NTG group, in which such a high score was observed in only 4.7% of subjects (OR 16.3, 95% CI 10.0-36.7; P < 0.0000001). CONCLUSIONS: An increased number of risk genetic variants, calculated both in a weighted or unweighted manner, significantly discriminates between the subjects with HTG and controls. Population-specific sets of SNPs included into the gene score seem to yield better discrimination power.
3rd Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czech Republic
Statistical Unit Institute for Clinical and Experimental Medicine Prague Czech Republic
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