| 1. |
|
|
| 2. |
|
|
| 3. |
- Fava, Cristiano, et al.
(författare)
-
Cardiovascular consequences of a polygenetic component of blood pressure in an urban-based longitudinal study: the Malmö Diet and Cancer.
- 2014
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 32:7, s. 1424-1428
-
Tidskriftsartikel (refereegranskat)abstract
- A recently published genome wide association study identified 29 single nucleotide polymorphisms (SNPs) influencing blood pressure (BP). Case-control studies suggest that a genetic risk score (GRS) based on these 29 SNPs affect the risk of cardiovascular disease (CVD), but its role for CVD at population level is unknown. Here, we prospectively evaluate the impact of this polygenetic BP component on CVD morbidity and mortality in a large urban-based middle-aged population.
|
|
| 4. |
- Fava, Cristiano, et al.
(författare)
-
Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome.
- 2009
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 27, s. 1794-1803
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test whether a previously hypertension-linked 23 cM region on chromosome 2 is linked to the metabolic syndrome (MetS) or its individual components, and whether a common I/D polymorphism of the adrenergic receptor 2b (ADRA2B) gene, mapping in that region, is associated with the same traits. METHODS: We conducted fine mapping of the hypertension-linked region on chromosome 2 spanning between 107 and 130 cM using 11 informative polymorphic markers in 260 healthy white siblings belonging to 118 nuclear families. Variance-component linkage analysis was performed for each MetS component and a composite sum of MetS phenotypes as quantitative trait after adjustment for significant covariates using 'Solar software package'. Successively, the I/D polymorphism of the ADRA2B gene was genotyped in 5283 patients in the Malmö Diet and Cancer-cardiovascular arm, seeking for association with the MetS using standard definitions and separately, with its individual components. RESULTS: For 24-h pulse pressure and waist/hip ratio, LOD [logarithm of the odds (to the base 10)] scores of more than two were found between 107 and 122 cM on chromosome 2. For the composite sum of MetS phenotypes, LOD score of more than 1 was found between 116 and 120 cM. There was no difference between carriers and noncarriers of the D-allele of the ADRA2B gene in MetS prevalence but D-carriers were associated with significantly higher levels of diastolic blood pressure. CONCLUSION: Our results suggest that chromosome 2 could harbor one or more genes implied in blood pressure homeostasis and MetS development. The ADRA2B I/D polymorphism is not consistently associated with MetS and metabolic/anthropometric parameters but with diastolic blood pressure in an urban-based population of middle-aged Swedes.
|
|
| 5. |
- Fava, Cristiano, et al.
(författare)
-
Determinants of kidney function in Swedish families: role of heritable factors.
- 2008
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 26:9, s. 1773-1779
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the determinants of kidney function and the role of heritable factors in a sample of 249 siblings free from known cardiovascular disease and without antihypertensive drugs belonging to 110 families. Four different measures and estimates of kidney function were considered. Blood pressure was recorded during 24 h by ambulatory blood pressure monitoring. Heritability was estimated with and without adjustment for significant covariates.In multivariate analysis, in addition to age, sex, BMI, HDL-cholesterol, 24-h systolic and mean blood pressure, systolic nocturnal blood pressure dipping resulted independently related to serum creatinine, estimated Cockcroft-Gault-creatinine clearance and estimated by the modification of diet in renal disease-glomerular filtration rate. After full adjustment, the heritability values were 51% for the measured creatinine clearance (P < 0.01), 58% for the estimated Cockcroft-Gault-creatinine clearance (P < 0.001), 40% for the estimated by the modification of diet in renal disease-glomerular filtration rate (P < 0.001), but 8% (P = 0.34) for serum creatinine.Our data confirm that kidney function is partially under genetic control and that genetic variants of importance for this trait could be mapped. The association of the circadian rhythm of blood pressure with kidney function in this sample deserves further investigation.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Fava, Cristiano, et al.
(författare)
-
Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.
- 2011
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 484-491
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden). METHODS: The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study. RESULTS: Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity. CONCLUSION: Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.
|
|
| 9. |
- Fava, Cristiano, et al.
(författare)
-
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
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 28:2, s. 294-299
-
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.
|
|
| 10. |
- Fava, Cristiano, et al.
(författare)
-
The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes.
- 2007
-
Ingår i: Journal of Hypertension. - 1473-5598. ; 25:1, s. 111-116
-
Tidskriftsartikel (refereegranskat)abstract
- Objective A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481 S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. Design and methods The cardiovascular cohort of the Malmo Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n = 6103, DNA available on n = 6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmo preventive Project (MPP) Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). Results Among individuals without AHT in the MIX study (n = 4988) there was no difference between carriers (n = 1164, 23%) and noricarriers (n = 3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P=0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the Ill and Ill studies (n = 2627) there was no difference between carriers (n = 607, 23%) and noricarriers (n = 2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from Ill to Ill Multivariate analysis gave no support of interaction between the CLC-Kb 481S polymorphism, gender, age or body mass index regarding their effect on BP. Conclusion Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.
|
|
