| 1. |
- Bengtsson Boström, Kristina, et al.
(author)
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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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In: J Hypertens. - 0263-6352. ; 25:4, s. 779-783
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Journal article (peer-reviewed)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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| 2. |
- Bøg-Hansen, Erik, et al.
(author)
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Predictors of acute myocardial infarction mortality in hypertensive patients treated in primary care.
- 2007
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 25:4, s. 237-243
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Journal article (peer-reviewed)abstract
- Objective. To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care. Design. Community-based cohort study. Setting. Hypertension outpatient clinic in primary health care. Subjects. Patients who consecutively underwent an annual follow-up during 1992-1993 (n =894; 377 men and 517 women). Methods. All events of fatal AMI were ascertained by record linkage to the National Mortality Register to December 31, 2002. Gender-specific predictors for AMI mortality were analysed by Cox regression. Main outcome measure. AMI mortality. Results. During a mean follow-up of 8.7 years 32 cases (8.5%) of fatal AMI were observed in men and 31 cases (6.0%) were observed in women. Most important predictors for AMI mortality in men were microalbuminuria (HR 3.8, CI 1.8-8.0) and left ventricular hypertrophy (HR 4.0, CI 1.7-9.4), whilst in women type 2 diabetes (HR 4.8, CI 2.4-9.8) was an important predictor. In hypertensive patients without diabetes male gender was associated with high AMI mortality (HR 2.7, CI 1.4-5.3), but in patients with both hypertension and type 2 diabetes the higher risk in men disappeared (HR 0.8, CI 0.4-1.7). Conclusion. Cardiovascular disease risk factors remain strong predictors of AMI mortality in hypertensive patients but with a different pattern in the two genders. Markers of organ damage are more important predictors in men, whereas markers of impaired glucose metabolism are more important predictors in women.
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| 3. |
- Dalemo, Sofia, et al.
(author)
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Diagnosis of patients with raised serum calcium level in primary care, Sweden.
- 2006
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In: Scandinavian journal of primary health care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 24:3, s. 160-5
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the diagnosis of hypercalcaemic patients and to evaluate whether frequent analyses of serum calcium can detect more patients with hypercalcaemia. DESIGN: Retrospective study of serum calcium analyses performed during the time period 1992-2000 and of the medical records of patients with elevated serum calcium levels between 1995 and 2000. SETTING: Primary care in Tibro, Sweden. SUBJECTS: Patients from the local community attending the primary healthcare centre. MAIN OUTCOME MEASURES: Frequency of serum calcium analyses, hypercalcaemic patients, and their diagnosis. RESULTS: Doubling the number of serum calcium analyses did not increase the detected number of raised calcium levels. On the other hand, more frequent parathyroid hormone (PTH) analyses resulted in a corresponding increase in detected high PTH levels. In Tibro, 15% (n = 22) of the patients with hypercalcaemia were diagnosed with primary hyperparathyroidism, giving a rate of 0.22%. This is comparable to the prevalence in other population studies. Over 40% (n = 9) of patients with primary hyperparathyroidism in the study had only slightly raised serum calcium levels (2.55-2.60 mmol/l). In 70% (n = 99) of the cases, the cause of hypercalcaemia was unknown. The second most common diagnosis was skeletal disorders followed by kidney disease. CONCLUSION: An increase in the number of serum calcium analyses did not result in increased detection of raised calcium levels. In contrast, an increase in the number of PTH analyses resulted in increased detection of primary hyperparathyroidism. Therefore, PTH analyses should be used more frequently.
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| 4. |
- Florez, Jose C., et al.
(author)
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The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people
- 2006
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:12, s. 3620-3624
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Journal article (peer-reviewed)abstract
- Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.
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| 5. |
- Hedner, Jan A, 1953, et al.
(author)
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Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study
- 2006
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 27:3, s. 564-70.
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Journal article (peer-reviewed)abstract
- Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI) >= 30 events center dot h(-1)) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.
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| 6. |
- Mehner, Anita, et al.
(author)
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Cholesterol in women at high cardiovascular risk is less successfully treated than in corresponding men
- 2008
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In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 64:8, s. 815-820
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Journal article (peer-reviewed)abstract
- Objective To assess the use of lipid-lowering therapy in patients with known coronary heart disease (CHD), cerebrovascular disease or diabetes in a community-based population in Sweden considering expert recommendations. Methods A random sample of individuals aged >= 40 years who were surveyed in 1993-1994 were revisited 10 years later during 2003-2004 (n=724). A clinical investigation focused on cardiovascular risk including serum total cholesterol. Information on medical history and current medication was collected in structured interviews. Results Eighty-two patients (11.3%) reported a history of CHD, including 51 men and 31 women. Fifty-three patients fulfilled criteria for treatment and most of them (85%) were on lipid-lowering therapy. A higher fraction of women were treated; however only 13% of them reached target cholesterol levels compared to 37% of the men (P<0.001). Sixty-five subjects (9.0%) had diabetes and/or a previous stroke (29 men, 36 women) but no previous CHD. Patients with CHD were more likely to be treated compared to patients with diabetes and/or stroke but no CHD (85.0 vs. 28.5%, OR 6.0, 95% CI 2.2-16.9, P=0.01). In a total of 79 participants (10.9%) who were on lipid-lowering therapy, women reached a total serum cholesterol level below 5.0 mmol/L less often than men (26.3 vs. 63.4%, P<0.001). Conclusions A considerable proportion of patients in primary care were untreated despite current guidelines on lipid-lowering therapy. Treatment outcome in women was less efficient compared with men. Strategies to improve pharmacological treatment in these patients should be developed.
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| 7. |
- Merlo, Juan, et al.
(author)
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Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families - a public health perspective
- 2006
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 7
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Journal article (peer-reviewed)abstract
- Background: Individuals belonging to the same family share a number of genetic as well as environmental circumstances that may condition a common SBP level. Among the genetic factors, the angiotensin converting enzyme (ACE) gene I/D polymorphism appears as a possible candidate as it might influence both SBP and the pharmacological effect of ACE inhibitors. We aimed to combine genetic epidemiology with public health ideas concerning life-course and multilevel epidemiology in order to understand the role of familial factors regarding individual SBP. Methods: We applied multilevel regression analysis on 1926 individuals nested within 438 families from South Sweden. Modelling familial SBP variance as a function of age and use of ACE inhibitors we calculates a variance partition coefficient and the proportional change in familial SBP variance attributable to differences in ACE gene I/D polymorphism. Results: Our results suggest the existence of genetic or environmental circumstances that produce a considerable familial clustering of SBP, especially among individuals using ACE-inhibitors. However, ACE gene I/D polymorphism seems to play a minor role in this context. In addition, familial factors - genetic, environmental or their interaction - shape SBP among non-users of ACE inhibitors but their effect is expressed later in the life- course. Conclusion: Strategies directed to prevent hypertension should be launched in younger rather than in older ages and both prevention of hypertension and its treatment with ACE inhibitors should be focused on families rather than on individuals.
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| 8. |
- Saxena, Richa, et al.
(author)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Journal article (peer-reviewed)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 9. |
- Winckler, Wendy, et al.
(author)
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Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes
- 2007
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 56:3, s. 685-693
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Journal article (peer-reviewed)abstract
- An important question in human genetics is the extent to which genes causing monogenic forms of disease harbor common variants that may contribute to the more typical form of that disease. We aimed to comprehensively evaluate the extent to which common variation irk the six known maturity-onset diabetes of the young (MODY) genes, which cause a monogenic form of type 2 diabetes, is associated with type 2 diabetes. Specifically, we determined patterns of common sequence variation in the genes encoding Gck, lpf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, respectively), selected a comprehensive set of 107 tag single nucleotide polymorphisms (SNPs) that captured common variation, and genotyped each in 4,206 patients and control subjects from Sweden, Finland, and Canada (including family-based studies and unrelated case-control subjects). All SNPs with a nominal P value < 0.1 for association to type 2 diabetes in this initial screen were then genotyped in an additional 4,470 subjects from North America and Poland. Of 30 nominally significant SNPs from the initial sample, 8 achieved consistent results in the replication sample. We found the strongest effect at rs757210 in intron 2 of TCF2, with corrected P values < 0.01 for an odds ratio (OR) of 1.13. This association was observed again in an independent sample of 5,891 unrelated case and control subjects and 500 families from the U.K., for an overall OR of 1.12 and a P value < 10(-6) in > 15,000 samples. We combined these results with our previous studies on HNF4 alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes susceptibility loci, and we found no genetic interactions between these six genes. We conclude that although rare variants in these six genes explain most cases of MODY, common variants in these same genes contribute very modestly, if at all, to the common form of type 2 diabetes.
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