Biomedical subjects

Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 19 recordsLinked to original sources

PubMed2006

Glucocorticoid receptor variant and risk of dementia and white matter lesions.

OBJECTIVE: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. METHODS: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. RESULTS: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. CONCLUSIONS: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.

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PubMed2006

Incidence and risk factors of disability in the elderly: the Rotterdam Study.

BACKGROUND: This study analyzed the incidence of disability and its risk factors in multiple dimensions in community-dwelling women and men of older age, between 1990 and 1999, in Rotterdam, The Netherlands. METHODS: For this community-based prospective longitudinal study, data were obtained from the Rotterdam Study that comprised a cohort of 7983 elderly who are 55 and over. The study sample for incident disability consisted of 4258 subjects who were disability free at baseline and had complete outcome data at follow-up, 6 years later. Sociodemographic factors, lifestyle variables, health conditions and disability status were assessed at baseline and follow-up. Disability was defined as a Disability Index (DI) > or =0.50 according to the Health Assessment Questionnaire. RESULTS: Multivariate analyses, performed separately due to gender differences, revealed that age, self-rated health, overweight, depression, joint complaints, medication use were predictors of disability for both men and women. Stroke, falling and presence of comorbidities predicted disability in men only while having a partner, poor cognitive functioning, osteoarthritis and morning stiffness only predicted disability in women. CONCLUSION: Identified risk factors in this study are to some extent modifiable, enabling interventive strategies, reckoning with gender differences in risk profile, in order to prevent disability.

Age Factors↗

PubMed2006

C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study.

PURPOSE: It remains unclear if inflammation itself may induce cancer, if inflammation is a result of tumor growth, or a combination of both exists. The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer. PATIENTS AND METHODS: A total of 7,017 participants age > or = 55 years from the Rotterdam Study were eligible for analyses. Mean follow-up time was 10.2 years. High-sensitivity CRP measurements were performed to identify additional values of 0.2 to 1.0 mg/L compared with standard procedures. Genotypes of the CRP gene were determined with an allelic discrimination assay. RESULTS: High levels (> 3 mg/L) of CRP were associated with an increased risk of incident cancer (hazard ratio, 1.4; 95% CI, 1.1 to 1.7) compared with persons with low levels (< 1 mg/L), even after a potential latent period of 5 years was introduced. Although CRP seems to affect several cancer sites, the association was strongest for lung cancer (hazard ratio, 2.8; 95% CI, 1.6 to 4.9). A CRP single nucleotide polymorphism associated with decreased CRP levels was associated with an increased lung cancer risk of 2.6 (95% CI, 1.6 to 4.4) in homozygous carriers. CONCLUSION: Baseline CRP levels seem to be a biomarker of chronic inflammation preceding lung cancer, even after subtracting a 5-year latent period. Furthermore, CRP gene variation associated with low CRP blood levels was relatively common in patients with lung cancer. Both chronic inflammation and impaired defense mechanisms resulting in chronic inflammation might explain these results.

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PubMed2006

The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe.

CONTEXT: Thyroid function has been related to Alzheimer disease (AD) and neuroimaging markers thereof. Whether thyroid dysfunction contributes to or results from developing AD remains unclear. Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help in elucidating the role of thyroid function in AD. OBJECTIVE: We investigated the association of recently identified polymorphisms in the DIO1 (D1a-C/T, D1b-A/G) and DIO2 (D2-ORFa-Gly3Asp, D2-Thr92Ala) genes with circulating thyroid parameters and early neuroimaging markers of AD. DESIGN AND PARTICIPANTS: The Rotterdam Scan Study is a population-based cohort study among 1,077 elderly individuals aged 60-90 yr. MAIN OUTCOME MEASURES: DIO1 and DIO2 polymorphisms and serum TSH, free T4, T3, and reverse T3 (rT3) levels were determined in 995 nondemented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging. RESULTS: Carriers of the D1a-T allele had higher serum free T4 and rT3, lower T3, and lower T3/rT3. The D1b-G allele was associated with higher serum T3 and T3/rT3. The DIO2 variants were not associated with serum thyroid parameters. No associations were found with hippocampal or amygdalar volume. CONCLUSION: This is the first study to report an association of D1a-C/T and D1b-A/G polymorphisms with iodothyronine levels in the elderly. Polymorphisms in the DIO1 and DIO2 genes are not associated with early magnetic resonance imaging markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or nonthyroidal illness rather than thyroid hormones being involved in developing AD.

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PubMed2006

Alpha-adducin polymorphism, atherosclerosis, and cardiovascular and cerebrovascular risk.

BACKGROUND AND PURPOSE: Carriers of the 460Trp allele of the alpha-adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease. We studied the association between the Gly460Trp polymorphism and atherosclerosis, cardiovascular disease, and cerebrovascular disease. METHODS: Intima-media thickness of the common carotid artery, as well as incident stroke and myocardial infarction, were studied within 6471 subjects of the Rotterdam Study. Within 1018 subjects of the Rotterdam Scan Study, prevalent silent brain infarcts and cerebral white matter lesions were studied. Subjects were grouped into 460Trp carriers (variant carriers) and homozygous carriers of the Gly460 allele (reference). RESULTS: Intima-media thickness of the common carotid artery was 0.80 mm in variant carriers compared with 0.79 mm in the reference group (P=0.04). Variant carriers had an increased risk of any stroke (hazard ratio [HR], 1.22; 95% CI, 1.02 to 1.45), ischemic stroke (HR, 1.29; 95% CI, 1.02 to 1.63), hemorrhagic stroke (HR, 1.07; 95% CI, 0.59 to 1.92), and of myocardial infarction (HR, 1.33; 95% CI, 1.05 to 1.69). For any ischemic stroke, there was a significant interaction between the Gly460Trp polymorphism and hypertension. Variant carriers more often had a silent brain infarct (odds ratio, 1.36; 95% CI, 0.98 to 1.88) and had more subcortical white matter lesions than the reference group (1.45 vs1.24 mL; P=0.22). CONCLUSIONS: The Gly460Trp polymorphism is associated with atherosclerosis, cardiovascular disease, and cerebrovascular disease, especially in hypertensive subjects.

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PubMed2006

Plasma pterins and folate in late life depression: the Rotterdam Study.

Tetrahydrobiopterin is a cofactor in the synthesis of monoamine neurotransmitters. High neopterin levels generally signal increased immune activation. Both pterins have been investigated in several small clinical studies of depressed patients with conflicting results. Therefore, we examined the relation of plasma biopterin and neopterin with depression in a population-based study. We also studied the association of pterins with folates in depressed persons as this vitamin is required for pterin biosynthesis. We screened 3884 adults aged 60 years and over for depressive symptoms. Screen positive subjects had a psychiatric interview to diagnose DSM-IV disorder. Plasma pterins and serum folate were determined in all persons with depressive symptoms (n=238) and randomly selected non-depressed persons (n=357). We found no association between the concentration of biopterin or neopterin with depressive symptoms or depressive disorders. However, in depressed persons the relation between pterins and folates was different than in the non-depressed, i.e. neopterin concentrations increased with folate levels in persons with depressive symptoms (0.09 per log(nmol/l folate); 95% CI=0.01, 0.18, P=0.03), but not in non-depressed persons (-0.07 per log(nmol/l folate); 95% CI=-0.17, 0.03, P=0.18). The interaction between depressive symptoms, folate and neopterin was significant (P=0.03). The study suggests that the relation between folate and pterins is altered in the depressed elderly.

Age of Onset↗

PubMed2006

TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study.

BACKGROUND AND PURPOSE: Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cardiovascular and cerebrovascular complications. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with a central role in inflammation. Little is known of the relation of variations within the gene and risk of cardiovascular and cerebrovascular disease. We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study. METHODS: Participants (N=6456) of the Rotterdam Study were included in the current study. Analyses of the relations of genotypes with the risk of myocardial infarction and stroke were performed according to Cox proportional-hazards methods. All analyses were adjusted for age, sex, conventional cardiovascular risk factors, and medical history. RESULTS: We found no association with the risk of myocardial infarction. A significantly increased risk of stroke was found, associated with the T allele of the -509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to 1.48). CONCLUSIONS: No association between the TGF-beta1 polymorphisms and myocardial infarction was observed; however, the -509 C/T and codon 10 Leu/Pro polymorphisms were associated with the risk of stroke.

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PubMed2006

High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study.

BACKGROUND: Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke. METHODS AND RESULTS: The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990-1993) were > or = 55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only. CONCLUSIONS: Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.

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PubMed2006

Lipoprotein-associated phospholipase A2 activity and risk of heart failure: The Rotterdam study.

AIMS: Evidence is accumulating that inflammation plays a role in the pathophysiology of heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties. We investigated whether Lp-PLA2 activity is associated with heart failure. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 subjects from the Rotterdam Study, a population-based cohort study among persons aged 55 years and over. During a mean follow-up of 6.7 years, 94 heart failure cases occurred. We excluded participants with heart failure or coronary heart disease at baseline and we accounted for incident coronary heart disease during follow-up. We used Cox proportional hazard models to compute hazard ratios adjusted for age, sex, non-HDL cholesterol, HDL cholesterol, body mass index, systolic blood pressure, diastolic blood pressure, hypertension, diabetes mellitus, smoking, and C-reactive protein. The hazard ratio per unit increase of Lp-PLA2 activity was 1.03 [95% confidence interval (95% CI 1.01-1.05]; P for trend was 0.011. Hazard ratios for the second, third, and fourth quartiles were 1.06 (95% CI 0.55-2.04), 1.43 (95% CI 0.73-2.81), and 2.33 (95% CI 1.21-4.49), respectively, using the lowest quartile of Lp-PLA2 activity as the reference category. CONCLUSION: This study suggests that Lp-PLA2 activity is independently associated with incident heart failure.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

High-dose testosterone is associated with atherosclerosis in postmenopausal women.

OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.

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PubMed2006

Association between calcification in the coronary arteries, aortic arch and carotid arteries: the Rotterdam study.

OBJECTIVE: The present study was performed to examine the prevalence of and associations between calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT), in an elderly population. METHODS AND RESULTS: This study was part of the population-based Rotterdam study. From October 2003 until July 2004, subjects underwent a 16-slice MSCT scan. Calcification was quantified by calculating the Agatston, volume and mass score. Current analyses were performed in 600 subjects (mean age 74 years). The prevalences of calcification in the coronary and carotid arteries were higher in men compared to women. However, aortic arch calcification was more prevalent among women. In men, correlation coefficients based on the Agatston score ranged from 0.40 (between coronary and aortic arch calcification) to 0.54 (between aortic arch and carotid calcification) (p<0.001). Correlation coefficients for women ranged from 0.30 (between coronary and aortic arch calcification) to 0.40 (between coronary and carotid calcification) (p<0.001). CONCLUSIONS: While the prevalences of calcification in the coronary and the carotid arteries were higher in men compared to women, aortic arch calcification was more prevalent among women. Moderate to strong correlations between calcification in different vessel beds were found.

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PubMed2006

Serum cholesterol levels and the risk of Parkinson's disease.

Several recent findings suggest a role of lipid and cholesterol metabolism in the pathogenesis of Parkinson's disease. Therefore, the authors examined the association between serum levels of cholesterol and the risk of Parkinson's disease in the prospective, population-based Rotterdam Study among 6,465 subjects aged 55 or more years with repeated in-person examination and on average 9.4 years of follow-up (1990-2004). Higher serum levels of total cholesterol were associated with a significantly decreased risk of Parkinson's disease (age- and sex-adjusted hazard ratio per mmol/liter increase in cholesterol = 0.77, 95% confidence interval: 0.64, 0.94), with evidence for a dose-effect relation. The association was restricted to women and remained unchanged after adjustment for multiple potential confounders. These findings may indicate a role of lipids in the pathogenesis of Parkinson's disease. Alternatively, they could reflect the strong correlation-especially in women-between levels of serum cholesterol and the antioxidant coenzyme Q10. If confirmed, this would provide further support for an important role of oxidative stress in the pathogenesis of Parkinson's disease.

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PubMed2006

Staphylococcus aureus nasal carriage is associated with glucocorticoid receptor gene polymorphisms.

The aim of this study was to determine whether polymorphisms of the glucocorticoid receptor gene, influencing glucocorticoid sensitivity, are associated with persistent nasal carriage of Staphylococcus aureus. Two nasal swab cultures were obtained from each of 2,929 participants. Subjects were classified as persistent carriers (n=563) if both cultures were positive. GG homozygotes of the exon 9beta polymorphism were associated with a 68% reduced risk of persistent S. aureus nasal carriage, whereas carriers of the codon 23 lysine allele displayed an 80% increased risk. Thus, genotype-dependent variation in the sensitivity to glucocorticoids is associated with tolerance toward staphylococcal nasal colonization.

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PubMed2006

Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Study.

PURPOSE: To investigate whether diabetes mellitus is a risk factor for open-angle glaucoma (OAG). DESIGN: Prospective population-based cohort study. PARTICIPANTS: Participants ages > or =55 years from the Rotterdam Study, The Netherlands. METHODS: Participants at risk for incident OAG (iOAG) underwent at baseline (1990-1993) and follow-up (1997-1999) the same ophthalmic examination including intraocular pressure (IOP) measurement, visual field testing, and simultaneous stereo optic disc photography. At baseline, diabetes mellitus was defined as the use of antidiabetic medication and/or a random or postload glucose value > or =11.1 mmol/l. The diagnosis of OAG was made with an algorithm based on optic disc measures and visual fields, independent of the IOP. MAIN OUTCOME MEASURE: Incident OAG. RESULTS: In total, 3837 participants without OAG at baseline were reexamined. After a mean follow-up time of 6.5 years, iOAG developed in 87 persons. The relative risk of iOAG associated with baseline diabetes was 0.82 (0.33-2.05). After adjustment for age, gender, follow-up time, IOP, IOP-lowering treatment, body mass index, and systemic hypertension, the relative risk of iOAG was 0.65 (0.25-1.64). CONCLUSIONS: In this prospective population-based study, diabetes mellitus was not a risk factor for OAG.

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PubMed2006

Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration.

CONTEXT: The evidence that inflammation is an important pathway in age-related macular degeneration (AMD) is growing. Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, and AMD. OBJECTIVES: To assess the associations between the CFH gene and AMD in the general population and to investigate the modifying effect of smoking, serum inflammatory markers, and genetic variation of C-reactive protein (CRP). DESIGN, SETTING, AND PARTICIPANTS: Population-based, prospective cohort study of individuals aged 55 years or older (enrollment between March 20, 1990, and July 31, 1993, and 3 follow-up examinations that were performed between September 1, 1993, and December 31, 2004) in Rotterdam, the Netherlands. The CFH Y402H polymorphism was determined in a total of 5681 individuals. Information on smoking, erythrocyte sedimentation rate, CRP serum levels, and haplotypes of the CRP gene were assessed at baseline. MAIN OUTCOME MEASURES: All severity stages of prevalent and incident AMD, graded according to the international classification and grading system for AMD. RESULTS: The frequency of CFH Y402H was 36.2% (4116/11,362 alleles). At baseline, there were 2062 persons (36.3%) with any type of AMD (prevalent cases), including 78 (1.4%) with late AMD (stage 4). During follow-up (mean, 8 years; median, 10 years), 1649 (35.5%) of 4642 participants progressed to a higher stage of AMD (incident cases), including 93 (5.6%) who developed late AMD. The odds ratio (OR) of AMD increased in an allele-dose manner with 2.00 (95% confidence interval [CI], 1.56-2.55) for stage 2 AMD, 4.58 (95% CI, 2.82-7.44) for stage 3 AMD, and 11.02 (95% CI, 6.82-11.81) for stage 4 (late, vision threatening) AMD for homozygous persons. Cumulative risks calculated by Kaplan-Meier analysis of late AMD by age 95 years were 48.3% for homozygotes, 42.6% for heterozygotes, and 21.9% for noncarriers. The population-attributable risk for CFH Y402H was 54.0%. Elevated erythrocyte sedimentation rates further increased the OR to 20.2 (95% CI, 9.5-43.0), elevated serum CRP levels to 27.7 (95% CI, 10.7-72.0), and smoking to 34.0 (95% CI, 13.0-88.6) for homozygotes compared with noncarriers without these determinants. The CRP haplotypes conferring high levels of CRP significantly increased the effect of CFH Y402H (P<.01). CONCLUSIONS: The CFH Y402H polymorphism may account for a substantial proportion of AMD in individuals similar to those in the Rotterdam Study and may confer particular risk in the presence of environmental and genetic stimulators of the complement cascade.

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PubMed2006

Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia.

OBJECTIVE: Inflammation plays a role in the pathogenesis of dementia and Alzheimer's disease (AD). Studies examining serum levels of C-reactive protein in relation to dementia yielded conflicting results. Since serum levels of C-reactive protein are partly determined by genetic factors, we examined the association between genetic variation in the C-reactive protein gene with dementia and AD. METHODS: This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly. Polymorphisms in the C-reactive protein gene (1184C>T, 2042C>T and 2911C>G) tagging the common haplotypes were genotyped and haplotypes were constructed. During follow-up (mean 9.2 years) 607 dementia cases were identified. We estimated the association between polymorphisms and haplotypes with dementia and AD with Cox' proportional hazard models. RESULTS: The T allele of the C-reactive protein 2042C>T polymorphism, related to lower serum levels of C-reactive protein, was associated with a lower risk of dementia and AD. This association was strongest in APOE epsilon4 allele carriers. CONCLUSION: These findings suggest that C-reactive protein plays a role in development of dementia.

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PubMed2006

The Generation R Study: Design and cohort profile.

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioral and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Of all eligible children at birth, 61% participate in the study. Data collection in the prenatal phase included physical examinations, questionnaires, fetal ultrasound examinations and biological samples. In addition, more detailed assessments are conducted in a subgroup of 1232 pregnant women and their children. The children form a prenatally recruited birth-cohort that will be followed until young adulthood. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

Adolescent↗

PubMed2006

The influence of the alpha-adducin G460W polymorphism and angiotensinogen M235T polymorphism on antihypertensive medication and blood pressure.

Despite the availability of a variety of effective antihypertensive drugs, inadequate control of blood pressure is common in hypertensive patients. The aim of this study was investigate whether the alpha-adducin G460W polymorphism or angiotensinogen M235T polymorphism has an effect on the mean difference in blood pressure in subjects using antihypertensive drugs. Data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, was used. This study started in 1990 and included 7983 subjects of 55 years and older. Data from three examination rounds were used. Subjects were included when their blood pressure was elevated at 1 or more examinations and/or a diuretic, beta-blocker, calcium antagonist, or ACE inhibitor was used. A marginal generalized linear model was used to assess the drug-gene interaction. In total, 3025 hypertensives were included. No drug-gene interaction on blood pressure levels was found. The mean difference in systolic blood pressure (SBP) between subjects with the W-allele and GG genotype of the alpha-adducin gene was for diuretic users 1.25 mmHg (95% CI:-2.86 to 5.35), for beta-blockers 0.02 mmHg (95% CI:-3.39 to 3.42), for calcium antagonists -0.70 mmHg (95% CI:-5.61 to 4.21), and for ACE inhibitors -3.50 mmHg (95% CI:-9.02 to 2.02). The mean difference in SBP between subjects with the TT and MM genotype was for diuretic users -2.33 mmHg (95% CI:-8.32 to 3.66), for beta-blocker -0.06 mmHg (95% CI:-4.91 to 4.79), for calcium antagonist 0.59 mmHg (95% CI:-5.95 to 7.13), and for ACE inhibitor -2.33 mmHg (95% CI:-9.66 to 5.01). The G460W polymorphism and the M235T polymorphism did not modify the difference in blood pressure levels among subjects who used diuretics, beta-blockers, calcium antagonists, or ACE inhibitors.

Adrenergic beta-Antagonists↗