| 11. |
- Grisoni, Marie-Lise, et al.
(författare)
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Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk : the MORGAM Project.
- 2009
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 10, s. 44-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the IL18 gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, IL18R1 and IL18RAP, with the risk of developing CVD. METHODS: Eleven tagging SNPs, 5 in IL18R1 and 6 in IL18RAP, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD. RESULTS: We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 IL18 SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful. CONCLUSION: Our analysis suggests that the variability of IL18R1 and IL18RAP genes are unlikely to contribute to modulate the risk of CVD.
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| 12. |
- Hughes, Maria F., et al.
(författare)
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Genetic Markers Enhance Coronary Risk Prediction in Men : The MORGAM Prospective Cohorts
- 2012
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Ingår i: PLOS ONE. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 7:7, s. e40922-
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Tidskriftsartikel (refereegranskat)abstract
- Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.
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| 13. |
- Janunger, Tomas, et al.
(författare)
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A novel stroke locus identified in a northern Sweden pedigree : linkage to chromosome 9q31-33.
- 2009
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 73:21, s. 1767-1773
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The population of northern Sweden is characterized by reduced genetic diversity and a high incidence of stroke. We sought to reduce genetic variation further, using genealogic analysis in a set of nuclear families affected by stroke, and we subsequently performed a genome-wide scan to identify novel stroke susceptibility loci. METHODS: Through genealogy, 7 nuclear families with a common ancestor, connected over 8 generations, were identified. A genome-wide scan using 449 microsatellite markers was performed with subsequent haplotype analyses. RESULTS: A maximum allele-sharing lod score of 4.81 on chromosome 9q31-q33 was detected. Haplotype analysis identified a common 2.2-megabase interval in the chromosomal region in 4 of the nuclear families, where an overrepresentation of intracerebral hemorrhage was observed. CONCLUSIONS: We have identified a novel susceptibility locus for stroke. Haplotype analysis suggests that a shared genetic factor is of particular importance for intracerebral hemorrhage.
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| 14. |
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| 15. |
- Johansson, Kristina, et al.
(författare)
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D-Dimer is associated with first-ever intracerebral hemorrhage : a nested case-control study
- 2018
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 49:9, s. 2034-2039
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.
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| 16. |
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| 17. |
- Karvanen, Juha, et al.
(författare)
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The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts.
- 2009
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Ingår i: Genetic Epidemiology. - : Wiley. - 0741-0395 .- 1098-2272. ; 33:3, s. 237-246
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Tidskriftsartikel (refereegranskat)abstract
- Recently, genome wide association studies (GWAS) have identified a number of single nucleotide polymorphisms (SNPs) as being associated with coronary heart disease (CHD). We estimated the effect of these SNPs on incident CHD, stroke and total mortality in the prospective cohorts of the MORGAM Project. We studied cohorts from Finland, Sweden, France and Northern Ireland (total N=33,282, including 1,436 incident CHD events and 571 incident stroke events). The lead SNPs at seven loci identified thus far and additional SNPs (in total 42) were genotyped using a case-cohort design. We estimated the effect of the SNPs on disease history at baseline, disease events during follow-up and classic risk factors. Multiple testing was taken into account using false discovery rate (FDR) analysis. SNP rs1333049 on chromosome 9p21.3 was associated with both CHD and stroke (HR=1.20, 95% CI 1.08-1.34 for incident CHD events and 1.15, 0.99-1.34 for incident stroke). SNP rs11670734 (19q12) was associated with total mortality and stroke. SNP rs2146807 (10q11.21) showed some association with the fatality of acute coronary event. SNP rs2943634 (2q36.3) was associated with high density lipoprotein (HDL) cholesterol and SNPs rs599839, rs4970834 (1p13.3) and rs17228212 (15q22.23) were associated with non-HDL cholesterol. SNPs rs2943634 (2q36.3) and rs12525353 (6q25.1) were associated with blood pressure. These findings underline the need for replication studies in prospective settings and confirm the candidacy of several SNPs that may play a role in the etiology of cardiovascular disease.
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| 18. |
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| 19. |
- Möllsten, Anna, et al.
(författare)
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Genetic polymorphisms in the renin-angiotensin system confer increased risk of stroke independently of blood pressure : a nested case-control study.
- 2008
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 26:7, s. 1367-1372
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The renin-angiotensin system has a pathophysiological role in cardiovascular disease through a variety of processes. Polymorphisms in involved genes have been described and implicated in stroke. The aim of this study was to investigate two polymorphisms in two genes in the renin-angiotensin system and the risk of stroke. DESIGN: A nested case-control study using baseline data obtained from population-based surveys in northern Sweden was performed. There were 275 individuals without major concomitant disease who suffered a first ever stroke during follow-up and 549 controls matched for age, sex and domicile. METHODS: Blood samples obtained at baseline were analyzed for potential risk factors including the A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene and the functional insertion/deletion polymorphism of the angiotensin-converting enzyme gene. RESULTS: Individuals with the AA genotype of the AT1R gene were at increased risk of ischemic stroke (odds ratio = 1.60; P = 0.005) compared with those with the AC and CC genotypes. The D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with a higher risk of stroke (odds ratio = 1.58; P = 0.014). CONCLUSION: In this prospective study, there was an association between A1166C polymorphism in the angiotensin II receptor gene and ischemic stroke. We also replicated previous observations that the D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with increased risk of stroke. The observed elevated stroke risks conferred by these two polymorphisms are independent of each other and common risk factors such as blood pressure, diabetes, smoking and high cholesterol levels.
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| 20. |
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