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- Ahluwalia, Tarunveer S, et al.
(författare)
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Uromodulin gene variant is associated with type 2 diabetic nephropathy.
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 1731-1734
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: About 35% of individuals with type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for microvascular complications like diabetic nephropathy. Recent genome-wide association studies have identified the uromodulin locus (UMOD), encoding the most common protein in human urine to be associated with hypertension and also with chronic kidney disease (CKD). In the present study we examined the association of the common variant of the uromodulin (UMOD) gene with type 2 diabetic nephropathy and kidney function. METHODS: UMOD variant rs13333226 was genotyped in a case-control material including 4888 unrelated type 2 diabetic individuals (n = 880 with and n = 4008 without nephropathy) from Sweden (Scania Diabetes Registry) using the ABI Real time TaqMan allelic discrimination assay. RESULTS: The G allele of rs13333226 was associated with a decreased risk of nephropathy [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001] after correction for confounding factors like age, sex, body mass index (BMI), blood pressure, kidney function, smoking and duration of diabetes. The same allele was also associated with a better kidney function [estimated glomerular filtration rate (eGFR), β = 0.117, P < 0.0001] and lower systolic blood pressure (β = -0.048, P = 0.013) in the overall study cohort. CONCLUSION/INTERPRETATION: The present study highlights that the common variant of the UMOD gene is protective against diabetic nephropathy susceptibility and also affects kidney function and blood pressure in patients with type 2 diabetes. However, the association with diabetic nephropathy was independent of blood pressure and kidney function.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Chittani, Martina, et al.
(författare)
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TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:6, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
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| 9. |
- Dahlberg, Jonas, et al.
(författare)
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Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 884-889
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Serum and glucocorticoid regulated kinase 1 (SGK1) expression is increased by aldosterone and is a key regulator of the amiloride-sensitive sodium channel (ENaC) in the distal nephron. We have previously shown that two SNPs in SGK1 (rs1057293 and rs1743966) are associated with blood pressure variation and blood pressure progression in the general population. Therefore, we tested the association of these variants with ischaemic stroke. METHODS: Using logistic regression, we analysed rs1057293 and rs1743966 for association with ischaemic stroke in two independent age-matched and sex-matched case-control groups from the twin cities of Lund (cases n = 1837 and controls n = 947) and Malmö (cases n = 888 and controls n = 893) in the Scania region of southern Sweden. RESULTS: In additive models adjusted for hypertension, smoking and diabetes, the major allele (G) of rs1057293 was associated (odds ratio, 95% confidence interval; P value) with ischaemic stroke with similar effect size in both studies; in Lund (1.35, 1.11-1.64; P = 0.002) and Malmö (1.30, 1.03-1.65; P = 0.027). When the two studies were pooled, the overall association was 1.32, 1.14-1.52; P < 0.001. The major allele of rs1743966 (A), which was in linkage disequilibrium with rs1057293, showed a similar trend as rs1057293 G-allele but with slightly weaker effect size and P value. CONCLUSION: In two independent but ethnically similar populations, we observed an association between genetic variants in SGK1 and ischaemic stroke. Interestingly, the association seems to be at least partially independent of blood pressure. This could imply that cerebrovascular ENaC or other SGK1-regulated proteins may be of importance for development of ischaemic stroke.
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