| 51. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 52. |
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| 53. |
- Enhörning, Sofia, et al.
(författare)
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Plasma copeptin and the risk of diabetes mellitus.
- 2010
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Ingår i: Circulation. - 1524-4539. ; 121:19, s. 51-2102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. METHODS AND RESULTS: We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). CONCLUSIONS: Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
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| 54. |
- Enhörning, Sofia, et al.
(författare)
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Relation between human vasopressin 1a gene variance, fat intake, and diabetes.
- 2009
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89:1, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Male arginine vasopressin 1a receptor knockout mice (V1aR(-/-)) display a phenotype of low triglycerides and high glucose concentrations and high-fat-diet-induced obesity and diabetes. OBJECTIVE: We investigated whether genetic variation of the human arginine vasopressin 1A (AVPR1A) gene is associated with phenotypic features resembling those of the V1aR(-/-) mouse. DESIGN: In a population-based cross-sectional study in southern Sweden, middle-aged individuals (n = 6055) were examined in 1991-1994. Associations between 4 AVPR1A tag single nucleotide polymorphisms (rs1042615, rs10784339, rs7308855, and rs10747983) and diabetes status, glucose and triglyceride concentrations, and BMI were analyzed. Furthermore, rs1042615 was related to diabetes status, glucose, and triglycerides within sex-specific quartiles of dietary fat intake (Q1(Fat)-Q4(Fat)) and BMI (Q1(BMI)-Q4(BMI)). RESULTS: Subjects carrying the T allele of rs1042615 had lower concentrations of triglycerides than did CC carriers (1.36 +/- 0.77 compared with 1.42 +/- 0.89 mmol/L; P = 0.014), especially in nondiabetic subjects (P = 0.001). Carriers of the rs1042615 T allele had higher fasting blood glucose (5.20 +/- 1.44 mmol/L compared with 5.12 +/- 1.22 mmol/L; P = 0.036) and a tendency toward an increased prevalence of diabetes (odds ratio: 1.22; 95% CI: 0.99, 1.51; P = 0.067) compared with CC carriers. The less common rs10784339, rs7308855, and rs10747983 were not consistently associated with metabolic variables. Among men, the rs1042615 T allele was associated with diabetes exclusively within Q4(Fat) (odds ratio: 2.22; 95% CI: 1.05, 4.71; P = 0.04) and Q4(BMI) (odds ratio: 1.81; 95% CI: 1.11, 2.93; P = 0.02). CONCLUSION: The rs1042615 T allele is associated with features resembling the phenotype of the V1aR(-/-) mouse, including uncoupling of the usual direct relation between glucose and triglycerides and an increased prevalence of diabetes in subjects with a high fat intake or who are overweight.
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| 55. |
- Fava, Cristiano, et al.
(författare)
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24-hour Ambulatory Blood Pressure is Linked to Chromosome 18q21-22 and Genetic Variation of NEDD4L Associates with Cross-Sectional and Longitudinal Blood Pressure in Swedes.
- 2006
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 70:3, s. 562-569
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Tidskriftsartikel (refereegranskat)abstract
- Numerous linkage studies have indicated chromosome 18q21–22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70–104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.
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| 56. |
- Fava, Cristiano, et al.
(författare)
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Association between adducin-1 G460W variant and blood pressure in Swedes is dependent on interaction with body mass index and gender.
- 2007
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 1941-7225 .- 0895-7061. ; 20:9, s. 981-989
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Tidskriftsartikel (refereegranskat)abstract
- Background: The W allele of the G460W polymorphism in the adducin-1 gene has been occasionally associated with increased blood pressure (BP). The aim of this study was to test whether the G460W variant is associated with BP levels and BP progression rate and whether G460W associations with BP are affected by sex, body mass index (BMI), or age. Methods: The G460W polymorphism was genotyped in the population-based Malmo Diet and Cancer-cardiovascular arm (MDC-CVA; n = 6103), of whom 53% had also been examined 11 +/- 4.4 years earlier in the Malmo Preventive Project (MPP). Results: Among subjects without antihypertensive treatment (AHT) in the MDC-CVA (n = 5009), there was no difference between carriers (38%) and noncarriers (62%) of the W allele in systolic BP (139.2 +/- 18.2 v 139.2 +/- 18.5 mm Hg; P = .99) or diastolic BP (85.9 +/- 9.1 v 86.1 +/- 9.2 mm Hg; P = .49). In subjects free from AHT in the MPP and MDC (n = 2637) there was no difference between carriers (38%) and noncarriers (62%) in progression of systolic BP (2.0 +/- 2.5 v 2.0 +/- 2.7 mm Hg/year; P = .45) or diastolic BP (0.59 +/- 1.6 v 0.56 +/- 1.5 mm Hg/year; P = .66) from MPP to MDC. At MDC-CVA BP was influenced by interaction between the G460W and BMI (P = .02 for systolic BP and P = .002 for diastolic BP) and by interaction between G460W and sex (P = .03 for systolic BP and P = .02 for diastolic BP), a result further confirmed by stratified analysis showing that female carriers of the W allele belonging to the upper tertile of BMI had increased systolic BP (146.1 +/- 18.6 v 141.2 +/- 18.6 mm Hg; P < .001), diastolic BP (88.7 +/- 8.7 v 86.1 +/- 8.7 mm Hg; P < .001), and prevalence of hypertension (72.5% v 61.8 %; P = .001). Conclusions: Our data suggest that the G460W polymorphism influences BP when BMI and sex are taken into account.
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| 57. |
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| 58. |
- Fava, Cristiano, et al.
(författare)
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Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872. ; 20:2, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The soluble epoxide hydrolase (gene name EPHX2) is responsible for metabolism of 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. There are several functional polymorphisms in the EPHX2 gene: two of them, the K55R and R287Q, showing an altered metabolic activity in vitro, were associated with coronary heart disease and ischemic stroke in previous studies. The aim of this study was to evaluate the effect of four polymorphisms in the EPHX2 gene on blood pressure levels, hypertension prevalence, and risk of incident cardiovascular events in a large sample of middle-aged Swedes. METHODS: The incidence of cardiovascular events (coronary events, n = 274; ischemic stroke, n = 197) was monitored over 10 years of follow-up. RESULTS: In the whole population, all polymorphisms had no effect on the studied parameters but a positive interaction between male sex and three SNPs including the K55R was evident: male, but not female, EPHX2 R55R homozygotes had significantly higher crude and adjusted systolic blood pressure and higher hypertension prevalence with respect to K-carriers. Kaplan-Meier curves showed higher incidence of ischemic strokes in male R55R homozygotes with respect to K-carriers (P = 0.015 by log-rank test). After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male R55R homozygotes remained significantly higher (hazard ratio: 4.8; 95% confidence interval: 1.2-19.9). CONCLUSION: The functional K55R polymorphism of the EPHX2 gene confers a higher risk of hypertension prevalence and increases the risk of incident ischemic stroke in male homozygotes. Additional studies are needed to confirm these data and to elucidate the interaction between sex and the EPHX2 K55R polymorphism.
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| 59. |
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| 60. |
- Fava, Cristiano, et al.
(författare)
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The common functional polymorphism -50G>T of the CYP2J2 gene is not associated with ischemic coronary and cerebrovascular events in an urban-based sample of Swedes.
- 2010
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Ingår i: Journal of Hypertension. - 1473-5598. ; 28:2, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CYP2J2 is responsible for the production of 5,6 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. It is abundantly expressed in human heart and also present in kidney and vasculature. Carriers of a common polymorphism, the CYP2J2-50G>T, rs890293, have reduced expression of CYP2J2 mRNA level in the heart putatively through the interference with a binding site for a transcription factor with consequently reduced circulating levels of CYP2J2 epoxygenase metabolites in vivo. AIM: The aim of the present study was to evaluate the effect of this functional polymorphism on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. METHODS: The CYP2J2 polymorphism was genotyped in 5740 participants of the cardiovascular cohort of the 'Malmö Diet and Cancer' study. The incidence of cardiovascular events (coronary events, n = 261; ischemic stroke, n = 185) was monitored over 10 years of follow-up. RESULTS: In the whole population the polymorphism had no effect on BP and hypertension prevalence and no interaction was found between the polymorphism and sex, age or body mass index. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke and coronary events was not significantly different in carriers of different genotypes. CONCLUSIONS: Our data do not support a major role for the CYP2J2-50G>T variant in determining BP level and incident ischemic events. Other studies are needed to elucidate if other polymorphisms in the same gene could have a role in BP homeostasis or incidence of cardiovascular events.
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