| 1. |
- Melander, Olle, et al.
(författare)
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Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension
- 2000
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Ingår i: Journal of Human Hypertension. - 1476-5527. ; 14:12, s. 819-823
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study was to identify variants in the 11BHSD2 gene and to test if such variants or the D16S496 are associated with primary hypertension, in Swedes. To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques. A polymorphism was identified in exon 3; G534A (Glu178Glu). This polymorphism and the D16S496 microsatellite were tested for association with primary hypertension in a population consisting of 292 patients with primary hypertension and 263 normotensive control subjects. The frequency of G534G homozygotes was higher in patients with primary hypertension than in normotensive control subjects (92.8% vs 87.8%; P < 0.05). The allele frequencies of the D16S496 microsatellite did not differ between the two groups (chi(2) = 11.0, df = 10; P = 0.36). In conclusion, over-representation of individuals homozygous for the G534 allele in hypertensive patients compared with control subjects suggests that a mutation in linkage disequilibrium with the G534A polymorphism could increase susceptibility to primary hypertension. Journal of Human Hypertension (2000) 14, 819-823
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| 2. |
- Melander, Olle, et al.
(författare)
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Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension
- 2000
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Ingår i: Hypertension. - 1524-4563. ; 36:3, s. 389-394
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Melander, Olle, et al.
(författare)
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Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians
- 2000
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Ingår i: Journal of Human Hypertension. - 1476-5527. ; 14:1, s. 43-46
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the alpha-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subjects from Finland to replicate the findings. The frequency of the Trp460 allele was lower in hypertensive patients than in normotensive controls in the Swedish population (17.7% vs 23.0%; P = 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in which the frequency of the Trp460 allele was significantly lower in hypertensive patients than in normotensive controls (17.0% vs 21. 7%; P = 0.02). In subjects who did not receive antihypertensive medication (n = 447) there was no difference between carriers of the three different codon 460 genotypes (Trp-Trp; Trp-Gly and Gly-Gly) either for systolic (128 +/- 18; 127 +/- 15 and 129 +/- 17 mm Hg, NS) or for diastolic blood pressure (75.6 +/- 12.1; 74.7 +/- 9.3 and 75.0 +/- 10.4 mm Hg, NS). In conclusion, the lower frequency of the Trp460 allele in hypertensive patients than in normotensive controls strongly argues against a pathogenic role of this allele in primary hypertension. The results rather suggest that another variant in linkage disequilibrium with the Gly460Trp polymorphism increases susceptibility for hypertension.Journal of Human Hypertension (2000) 14, 43-46.
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| 4. |
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| 5. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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| 6. |
- Bari, Muhammad Rizuanul, et al.
(författare)
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Abdominal obesity and insulin resistance in patients with type 2 diabetes in a Swedish community - Skaraborg Hypertension and Diabetes Project
- 2006
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 24:4, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore the association between abdominal obesity and insulin resistance in patients with type 2 diabetes. Design. A cross-sectional observational study. Setting. Primary care in Skara, Sweden. Subjects. A total of 198 men and 186 women with type 2 diabetes who consecutively completed an annual check-up in 1992-1993. Main outcome measures. Abdominal obesity was defined according to criteria for the metabolic syndrome using the waist circumference (WC): > 102 cm for men and > 88 cm for women. Insulin resistance was estimated using the Homeostasis Model Assessment (HOMA), and was dichotomized by the 75th percentile (IR). Results. Abdominal obesity was found in 66 men (33%), and in 106 women (57%). Pearson's correlation coefficients between components of the metabolic syndrome and IR were statistically significant for WC, waist-hip ratio, serum triglycerides, and HDL cholesterol, and were higher for WC (0.40) than for waist-hip ratio (0.23) in both genders (p < 0.001). The association between WC and IR was challenged by successively entering other components of the metabolic syndrome into the model in a logistic regression. In the final model, adjusting for differences in age, systolic blood pressure, HbA1c, serum triglycerides, HDL cholesterol, and microalbuminuria, the association remained statistically significant both in men (OR 8.6, 95% CI 3.0-25.2, p < 0.001), and in women (OR 5.6, 95% CI 1.7-18.1, p = 0.004). Conclusions. WC provides a feasible measure for insulin resistance in the vast majority of subjects with type 2 diabetes. It is convenient and less expensive than direct means and could be used as a proxy for insulin resistance in population studies.
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| 7. |
- Beckman, Anders, et al.
(författare)
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The role country of birth plays in receiving disability pensions in relation to patterns of health care utilisation and socioeconomic differences: a multilevel analysis of Malmo, Sweden
- 2006
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: People of low socioeconomic status have worse health and a higher probability of being granted a disability pension than people of high socioeconomic status. It is also known that public and private general physicians and public and private specialists have varying practices for issuing sick leave certificates ( which, if longstanding, may become the basis of disability pensions). However, few studies have investigated the influence of a patient's country of birth in this context. Methods: We used multilevel logistic regression analysis with individuals ( first level) nested within countries of birth ( second level). We analysed the entire population between the ages of 40 and 64 years ( n = 80 212) in the city of Malmo, Sweden, in 2003, and identified 73% of that population who had visited a physician at least once during that year. We studied the associations between individuals and country of birth socioeconomic characteristics, as well as individual utilisation of different kinds of physicians in relation to having been granted a disability pension. Results: Living alone ( ORwomen = 1.72, 95% CI: 1.62 - 1.82; ORmen = 2.64, 95% CI: 2.46 - 2.83) and having limited educational achievement (ORwomen = 2.14, 95% CI: 2.00 - 2.29; ORmen = 2.12, 95% CI: 1.98 - 2.28) were positively associated with having a disability pension. Utilisation of public specialists was associated with a higher probability (ORwomen = 2.11, 95% CI: 1.98 - 2.25; ORmen = 2.16, 95% CI: 2.01 - 2.32) and utilisation of private GPs with a lower probability (ORmen = 0.76, 95% CI: 0.69 - 0.83) of having a disability pension. However, these associations differed by countries of birth. Over and above individual socioeconomic status, men from middle income countries had a higher probability of having a disability pension (ORmen = 1.61, 95% CI: 1.06 - 2.44). Conclusion: The country of one's birth appears to play a significant role in understanding how individual socioeconomic differences bear on the likelihood of receiving a disability pension and on associated patterns of health care utilisation.
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| 8. |
- Bengtsson Boström, Kristina, et al.
(författare)
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Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension
- 2007
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Ingår i: J Hypertens. - 0263-6352. ; 25:4, s. 779-783
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case-control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.
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| 9. |
- Bengtsson Boström, Kristina, et al.
(författare)
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Polymorphism in the angiotensin converting enzyme but not in the angiotensinogen gene is associated with hypertension and type 2 diabetes: the Skaraborg Hypertension and diabetes project
- 1999
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Ingår i: Journal of Hypertension. - 1473-5598. ; 17:11, s. 1569-1575
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the association between polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene and hypertension and/or type 2 diabetes in a community population. PATIENTS AND METHODS: The insertion (I)/deletion (D) polymorphism of the ACE gene and the M235T polymorphism of the AGT gene were genotyped in 773 nondiabetic individuals with hypertension, 193 normotensive patients with type 2 diabetes, 243 patients with type 2 diabetes and hypertension, and in 820 normotensive control individuals identified in a community-based study. RESULTS: The DD genotype was associated with hypertension in individuals less than 70 years [odds ratio (OR) = 1.54, confidence interval (CI) = 1.09-2.18] and remained so when patients with type 2 diabetes were excluded from the analysis (OR = 1.45, CI = 1.01-2.09). The strongest association was with the combination of type 2 diabetes and hypertension (OR = 2.19, CI = 1.09-4.38). There was no association with type 2 diabetes without hypertension. No association was observed between the M235T variant or the 3'-microsatellite polymorphism of the AGT gene and hypertension. CONCLUSION: The D-allele of the ACE gene ID polymorphism increases susceptibility to hypertension, particularly when associated with type 2 diabetes. No association was observed between the M235T variant or 3'-microsatellite polymorphism of the AGT gene and hypertension.
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| 10. |
- 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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