| 1. |
- Bengtsson Boström, Kristina
(author)
-
Genetic Factors Contributing to Hypertension. With Emphasis on Hypertension in Type 2 Diabetes
- 2002
-
Doctoral thesis (other academic/artistic)abstract
- The causes of hypertension (HT) and type 2 diabetes (T2DM) are mainly unknown, but they arise from interplay between several genetic and environmental factors. The aim of this thesis was to investigate whether polymorphisms in putative candidate genes for HT increase the susceptibility to HT and/or T2DM. The DD genotype of the angiotensin converting enzyme (ACE) gene I/D polymorphism was associated with HT in a large population-based study from Skara, Sweden, particularly with HT combined with T2DM in lean patients less than 70 years. Further, the D allele increased mortality in male patients with HT and T2DM. Three polymorphisms in the angiotensinogen gene were not found to be associated with HT and/or T2DM. A novel association between hypertension and the Arg389Arg genotype of the Arg389Gly polymorphism in the beta 1 adrenergic receptor (B1AR) gene was shown in a case-control study from southern Sweden. The Arg389Arg genotype conferred higher diastolic blood pressure levels and increased heart rate in genotype discordant sibling pairs from Finland. Finally, the Arg16 and Gln27 alleles of the Arg16Gly and Gln27Glu polymorphisms in the beta 2 adrenergic receptor (B2AR) gene were shown to be associated with hypertension combined with T2DM. The Arg16 allele conferred higher systolic blood pressure levels and higher body mass index in genotype discordant sibling pairs. In conclusion, the ACE gene DD genotype increases the susceptibility to HT and ID and DD genotypes confer an increased risk of mortality. Genetic variants of B1AR and B2AR genes influence blood pressure and increase susceptibility for HT.
|
|
| 2. |
- Melander, Olle, et al.
(author)
-
Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension
- 2000
-
In: Hypertension. - 1524-4563. ; 36:3, s. 389-394
-
Journal article (peer-reviewed)abstract
- Gitelman's syndrome is an autosomal recessive disorder characterized by electrolyte disturbances and low blood pressure. The disease is caused by homozygous or compound heterozygous inactivating mutations in the thiazide-sensitive NaCl-cotransporter gene leading to reduced renal sodium reabsorption. We report 4 patients with Gitelman's syndrome from southern Sweden, all in whom we identified compound heterozygous mutations in the thiazide-sensitive NaCl-cotransporter gene (Gly439Ser, Gly731Arg, Gly741Arg, Thr304Pro, and 2745insAGCA), of which the latter 2 have not been described before. We hypothesized that such mutations in their heterozygous form protect against primary hypertension in the general population and that the gene may also harbor activating mutations that increase the risk for primary hypertension. Accordingly, the gene was screened for mutations in 20 patients with primary hypertension and in 20 normotensive subjects by single-strand conformation polymorphism and direct DNA sequencing. The Arg904Gln, Gly264Ala, and C1420T variants, found in the mutation screening of subjects without Gitelman's syndrome, were studied further. Population genotype frequencies were determined in 292 unrelated patients with primary hypertension and 264 unrelated normotensive subjects from southern Sweden. Gln904 homozygotes were overrepresented in hypertensive patients compared with normotensive subjects (5 of 292 versus 0 of 264; P:=0.03). In conclusion, we confirm that Gitelman's syndrome is caused by mutations in the thiazide-sensitive NaCl-cotransporter gene. Our results further suggest that subjects homozygous for the Gln904 variant have an increased risk for development of primary hypertension.
|
|
| 3. |
|
|
| 4. |
- Wowern, Fredrik, et al.
(author)
-
A Functional Variant in the {alpha}2B Adrenoceptor Gene, a Positional Candidate on Chromosome 2, Associates With Hypertension.
- 2004
-
In: Hypertension. - 1524-4563. ; 43:592, s. 592-597
-
Journal article (peer-reviewed)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.
|
|
