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- 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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- Torffvit, Ole, et al.
(författare)
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Urinary excretion rate of tamm-horsfall protein is related to salt intake in humans.
- 2004
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Ingår i: Nephron Physiology. - : S. Karger AG. - 1660-2137. ; 97:1, s. 6-31
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Increased salt intake and enhanced salt sensitivity are implicated in the pathogenesis of hypertension. The aim of the present study was to investigate whether the urinary excretion rate of Tamm-Horsfall protein (THP) is dependent on salt intake in healthy, genetically hypertension-prone individuals. <i>Methods:</i> Thirty unrelated subjects (13 men and 17 women, mean age 48.1 ± 6.7 years) with at least one first-degree relative with primary hypertension were studied. After a baseline investigation, the study subjects were put on a low-salt diet (10 mmol of sodium and 70 mmol of potassium per day) for 1 week. During the second week, sodium chloride capsules (230 mmol/day) were added to the diet to achieve a high-salt intake of 240 mmol/day. Urine samples (24-hour and overnight collections) were collected before the baseline investigation and at the end of the high- and low-salt diet weeks. The salt sensitivity was calculated as the difference between the blood pressure during high salt intake and the blood pressure during low salt intake. <i>Results:</i> A low salt intake induced a decrease in the urinary excretion rate of THP during the night (11.7 µg/min) compared with baseline (19.5 µg/min; p < 0.05) and high salt intake (23.1 µg/min; p < 0.01). Furthermore, a greater response in blood pressure to a high salt intake, i.e. high salt sensitivity, was associated with increased excretion of THP in urine during the change to high salt intake (r = 0.38, p < 0.05). <i>Conclusion:</i> We were able to confirm that urinary excretion of THP is dependent on sodium intake. Patients with a high salt sensitivity, i.e. an exaggerated blood pressure response to high salt intake, responded to the high salt intake with an even greater increase in the urinary excretion rate of THP. The mechanism underlying this response is still unknown, but it might indicate that distal nephron function in healthy, genetically hypertension-prone individuals is altered.
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- Wowern, Fredrik, et al.
(författare)
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A Functional Variant in the {alpha}2B Adrenoceptor Gene, a Positional Candidate on Chromosome 2, Associates With Hypertension.
- 2004
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Ingår i: Hypertension. - 1524-4563. ; 43:592, s. 592-597
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan in Scandinavians, we found suggestive linkage between early-onset primary hypertension and a region on chromosome 2. The 2B-adrenoceptor gene, a candidate gene within this region, harbors a functional insertion/deletion (I/D) polymorphism of three glutamate residues. The aim of this study was to investigate if the DD genotype is associated with hypertension in Swedes. We performed an association study between the I/D polymorphism of the 2B-adrenoceptor and hypertension in the Skaraborg population. The material consists of all known patients with primary hypertension in Skara (n772 nondiabetic subjects; n171 normoalbuminuric type 2 diabetic subjects) and 817 population control subjects. We first compared genotype frequencies between patients with early-onset hypertension (aged 50 years or younger at onset) and subjects with normotension (blood pressure 120/80 mm Hg). Thereafter, the polymorphism was tested for association with hypertension at the population level. When comparing patients with early-onset hypertension and normotensive subjects, the DD versus II genotype was associated with early-onset hypertension when diabetic subjects were excluded from the analysis (OR2.0; 95% CI1.2 to 3.5) or when they were not excluded (OR1.8; 95% CI1.0 to 3.1). At the population level, the DD versus II genotype was weakly associated with nondiabetic hypertension (OR1.4; 95% CI1.0 to 1.8). Our data suggest that carriers of the DD versus II genotype of the 2B-adrenoceptor are at increased risk for hypertension. The genotypic effect is most evident when comparing groups corresponding to the upper and lower tails of the blood pressure distribution in the population; however, in nondiabetic hypertensive subjects it is weakly detectable even at the population level.
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