| 1. |
- Bengtsson Boström, Kristina, et al.
(författare)
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Polymorphisms in α- And β-adrenergic receptor genes, hypertension, and obstructive sleep apnea : The skaraborg sleep study
- 2010
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Ingår i: International Journal of Hypertension. - : Hindawi Limited. - 2090-0384 .- 2090-0392. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α 2B -, β 1 -, and β 2 -adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β 1 -adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02-4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95 CI 1.4-21.2).
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| 2. |
- Boström, Kristina Bengtsson, et al.
(författare)
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Polymorphisms in alpha - and betaadrenergic receptor genes, hypertension and obstructive sleep apnea. The Skaraborg Sleep Study. J Hypertension
- 2010
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Ingår i: International Journal of Hypertension. - 2090-0392. ; 2010:Art ID 458410
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Tidskriftsartikel (refereegranskat)abstract
- The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α(2B)-, β(1)-, and β(2)-adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β(1)-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02-4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4-21.2).
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| 5. |
- 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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| 6. |
- Fava, Cristiano, et al.
(författare)
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Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome.
- 2009
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Ingår i: Journal of Hypertension. - 1473-5598. ; 27, s. 1794-1803
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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.
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| 8. |
- Koivukoski, Liisa, et al.
(författare)
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Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.
- 2004
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 13:19, s. 2325-2332
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Tidskriftsartikel (refereegranskat)abstract
- Individual genome-wide scans of blood pressure (BP) and hypertension (HT) have shown inconsistent results. The aim of this study was to investigate whether there was any consistent evidence of linkage across multiple studies with similar ethnicity. We applied the genome-search meta-analysis method (GSMA) to nine published genome-wide scans of BP (n=5) and HT (n=4) from Caucasian populations. For each study, the genome was divided into 120 bins and ranked according to the maximum evidence of linkage within each bin. The ranks were summed and averaged across studies and significance levels were estimated, on the basis of a distribution function of summed ranks or permutation tests without (P-U) or with (P-W) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (P-U=0.0001 and P-W=0.0001), diastolic BP (DBP) (P-U=0.007 and P-W=0.02), HT and DBP pooled (P-U=0.00002 and P-W=0.0001) and HT and systolic BP (SBP) pooled (P-U=0.0003 and P-W=0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (P-U=0.003 and P-W=0.009), DBP (P-U=0.05 and P-W=NS), HT and DBP pooled (P-U=0.001 and P-W=0.004) and HT and SBP pooled (P-U=0.001 and P-W=0.005). The summed ranks of the HT analysis correlated significantly with those of the DBP (r=0.20, P=0.03) but not with those of the SBP. Both loci showed clustering of significant bins in the analysis of HT and DBP. We conclude that modest or non-significant linkage on chromosomes 3p14.1-q12.3 and 2p12-q22.1 in each individual study translates into genome-wide significant or highly suggestive linkages to HT and DBP in our GSMA analysis.
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| 9. |
- Melander, Olle, et al.
(författare)
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Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma.
- 2007
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Ingår i: Journal of Hypertension. - 1473-5598. ; 25:3, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Objective The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, crossover design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity. Methods Participants received all meals and drinks with a total daily NaCl content of 50 mmol during 8 weeks. In addition, NaCl capsules (1100 mmol/day) and corresponding placebo capsules were administered for 4 weeks each in random order. ABP after high-salt intake (1150 mmol/day) was compared with ABP after low-salt intake (50 mmol/ day). Salt sensitivity was defined as the difference between 24-h systolic ABP at the high-salt versus the low-salt periods. Baseline renin and Nt-proANP were related to salt sensitivity. Results Lowering of salt intake from 150 to 50 mmol/day induced significant blood pressure reductions (mean reduction, 95% confidence interval) in systolic and diastolic 24-h ABP (5.8, 3.4-8.2 and 2.6, 0.91 -4.4 mmHg), daytime ABP (5.5, 2.9-8.1 and 2.3, 0.42-4.1 mmHg) and night-time ABP (6.4, 3.5-9.3 and 3.4, 1.4-5.5 mmHg). Baseline In(renin) correlated inversely with salt sensitivity (r = -0.50, P = 0.001) whereas baseline In(Nt-proANP) correlated directly (r = 0.33, P = 0.04). Conclusion Lowering of salt intake with 100 mmol/day induces clinically relevant ABP reductions. Renin and Nt-proANP, measured with individuals on their habitual diet, could be useful biomarkers to identify individuals with the greatest blood pressure-lowering benefit from reduced salt intake.
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