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- Fava, Cristiano, et al.
(author)
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Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome.
- 2009
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In: Journal of Hypertension. - 1473-5598. ; 27, s. 1794-1803
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Journal article (peer-reviewed)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.
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| 2. |
- Fava, Cristiano, et al.
(author)
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Determinants of kidney function in Swedish families: role of heritable factors.
- 2008
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In: Journal of Hypertension. - 1473-5598. ; 26:9, s. 1773-1779
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Journal article (peer-reviewed)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.
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| 3. |
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| 4. |
- Fava, Cristiano, et al.
(author)
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The V433M Variant of the CYP4F2 Is Associated With Ischemic Stroke in Male Swedes Beyond Its Effect on Blood Pressure.
- 2008
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In: Hypertension. - 1524-4563. ; 52, s. 373-380
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Journal article (peer-reviewed)abstract
- Cytochrome (CYP) 4A11 and CYP4F2 are responsible for renal production of 20-hydroxyeicosatetraenoic acid, a vasoconstrictor and natriuretic substance. The CYP4A11 F434S and CYP4F2 V433M polymorphisms reduce 20-hydroxyeicosatetraenoic acid production in vitro. The aim of the present study was to evaluate the effect of these polymorphisms on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. The polymorphisms were genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study. The incidence of cardiovascular events (coronary events, n=276; ischemic stroke, n=199) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment. In the whole population, CYP4A11 S434S homozygotes had higher systolic BP, both crude and adjusted for the number of antihypertensive drugs, and higher prevalence of hypertension with respect to F434 carriers. Male, but not female, CYP4F2 M433 carriers had significantly higher crude and adjusted systolic and diastolic BPs and a trend toward higher hypertension prevalence (P=0.06) with respect to V433V homozygotes. After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male CYP4F2 M433 carriers was significantly higher with respect to V433V homozygotes (hazard ratio: 1.69; 95% CI: 1.10 to 2.60) even when baseline BP levels and hypertension prevalence were included in the Cox proportional hazard model. A common CYP4F2 V433M polymorphism might increase the risk of incident ischemic stroke in male subjects only partially through its elevating effect on BP. Additional studies are needed to confirm these data.
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