Archive for the ‘Scientific publication’ Category
woensdag, december 7th, 2011
| Title | The role of the cytochrome P450 3A5 enzyme for blood pressure regulation in the general Caucasian population |
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| Year | 2005 |
| Estimated date | 2005-05-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | Cytochrome P450 3A (CYP3A) enzymes are important for
drug metabolism in gut and liver. The CYP3A5 isoenzyme
is also expressed in the kidney and has been implicated in
renal sodium reabsorption and blood pressure regulation.
Its expression and activity is strongly linked to a polymorphism
(i.e. 6986G> A). Thus, appreciable expression is
found in carriers of the CYP3A5*1 (6986A) but not in
homozygous carriers of the CYP3A5*3 (6986G) allele. We
tested whether the presence of CYP3A5*1 affects blood
pressure in Caucasian individuals who were enrolled in the
Prevention of REnal and Vascular ENd stage Disease
(PREVEND) study. In addition, we evaluated whether the
genetic effect of CYP3A5*1 on blood pressure is modulated
by sodium intake. CYP3A5*1 was found in 13.3% (901
individuals) of the cohort (6777 individuals). Diastolic blood
pressure was not affected by CYP3A5*1. Overall, systolic
and pulse pressure were significantly lower in carriers of
CYP3A5*1, both after univariate analysis adjusted for age
(P = 0.012 and P = 0.008) and in logistic regression analysis
(P = 0.015 and P = 0.012). The effect on systolic blood
pressure was significantly modulated by sodium intake
(P = 0.038). In separate analysis according to gender,
CYP3A5*1 accounted for a significant age adjusted
decrease in systolic blood pressure ( – 1.6 mmHg, P= 0.04)
and pulse pressure ( – 1.2 mmHg, P = 0.04) in females but
not in men. The present study demonstrates that the
CYP3A5*1 allele affects systolic blood pressure and pulse
pressure in the general population. Its role in hypertensive
disease and potential gender differences should be
investigated in further studies. Pharmacogenetics and
Genomics 15:831–837 c 2005 |
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Tags: 2005, None, Scientific Publication, The role of the cytochrome P450 3A5 enzyme for blood pressure regulation in the general Caucasian population
Posted in Scientific publication | Reacties uitgeschakeld
woensdag, december 7th, 2011
| Title | LPS-Induced Expression of a Novel Chemokine Receptor (L-CCR) in Mouse Glial Cells In Vitro and In Vivo |
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| Year | 2003 |
| Estimated date | 2001-12-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | ABSTRACT There is increasing evidence that chemokines, specialized regulators of
the peripheral immune system, are also involved in the physiology and pathology of the
CNS. It is known that glial cells (astrocytes and microglia) express various chemokine
receptors like CCR1, -3, -5, and CXCR4. We have investigated the possible expression of
the known CC chemokine receptors (CCR1–8 and D6) in murine glial cells. In addition,
we examined possible glial expression of the orphan CC chemokine receptor L-CCR that
has been identified previously in murine macrophages. We report here expression of
L-CCR mRNA in murine astrocytes and microglia. Furthermore, L-CCR mRNA expression
was strongly induced after application of bacterial lipopolysaccharide (LPS), both in
vitro and in vivo. Functional studies and binding experiments using biotinylated monocyte
chemoattractant protein (MCP)-1 (CCL2) indicate that CCL2 could be a candidate
chemokine ligand for glial L-CCR. Based on the data presented, it is suggested that
L-CCR is a functional glial chemokine receptor that is important in neuroimmunology.
GLIA 41:327–336, 2003. |
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Tags: 2003, LPS-Induced Expression of a Novel Chemokine Receptor (L-CCR) in Mouse Glial Cells In Vitro and In Vivo, None, Scientific Publication
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woensdag, december 7th, 2011
| Title | CCR5 Deletion Protects Against Inflammation- Associated Mortality in Dialysis Patients |
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| Year | 2009 |
| Estimated date | 2009-04-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion
variant of the CCR5 gene (CCR532) leads to deficiency of the receptor. We hypothesized that CCR532
modulates inflammation-driven mortality in patients with ESRD. We studied the interaction between CCR5
genotype and levels of high-sensitivity C-reactive protein (hsCRP) in 603 incident dialysis patients from the
multicenter, prospective NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort.
CCR5 genotype and hsCRP levels were both available for 413 patients. During 5 yr of follow-up, 170 patients
died; 87 from cardiovascular causes. Compared with the reference group of patients who had the wild-type
CCR5 genotype and hsCRP 10 mg/L (n 225), those carrying the deletion allele with hsCRP 10 mg/L
(n 55) had similar mortality, and those carrying the wild-type genotype with hsCRP 10 mg/L (n 108)
had an increased risk for mortality (HR: 1.82; 95% CI: 1.29 to 2.58). However, those carrying the deletion allele
with hsCRP 10 mg/L (n 25) had a mortality rate similar to the reference group; this seemingly protective
effect of the CCR5 deletion was even more pronounced for cardiovascular mortality. We replicated these
findings in an independent Swedish cohort of 302 ESRD patients. In conclusion, the CCR532 polymorphism
attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD.
J Am Soc Nephrol 20: 1641–1649, 2009. doi: 10.1681/ASN.2008040432 |
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Tags: 2009, CCR5 Deletion Protects Against Inflammation- Associated Mortality in Dialysis Patients, None, Scientific Publication
Posted in Scientific publication | Reacties uitgeschakeld
woensdag, december 7th, 2011
| Title | Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8 |
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| Year | 2003 |
| Estimated date | 2002-08-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | Abstract: It has become clear in the past years
that chemokines and chemokine receptors are pivotal
regulators of cellular communication and trafficking.
In addition to the 20 chemokine receptors
that have been cloned and described, various
orphan receptors with a chemokine receptor-like
structure are known. We have investigated the orphan
mouse chemokine receptor (L-CCR) in HEK
293 cells, a receptor that was originally described
in a mouse macrophage cell line. Cells expressing
this receptor show pertussis toxin-sensitive chemotaxis
and small intracellular calcium transients in
response to the chemokines CCL2, CCL7, CCL8,
and CCL5. Biotinylated CCL2 binds to L-CCRexpressing
cells, and transfection experiments with
an L-CCR–green fluorescent protein fusion protein
showed L-CCR expression in the membranes of
recombinant HEK 293 cells. Although radioligand
binding was not detected, it is suggested that LCCR
is a functional chemokine receptor. J. Leukoc.
Biol. 74: 243–251; 2003. |
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Tags: 2003, Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8, None, Scientific Publication
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woensdag, december 7th, 2011
| Title | An Increased Coronary Risk Is Paradoxically Associated with Common Cholesteryl Ester Transfer Protein Gene Variations That Relate to Higher High-Density Lipoprotein Cholesterol: A Population-Based Study |
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| Year | 2006 |
| Estimated date | 2006-03-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | Background: Several cholesteryl ester transfer protein (CETP) polymorphisms
affect high-density lipoprotein (HDL) cholesterol, but the
impact of CETP gene variants on incident coronary disease in the
general population is uncertain after correction for their effect on
HDL cholesterol.
Design: We determined relationships between the CETP 629C3A
promoter (n 8141), the TaqIB (n 8289), and the I405V (n 8265)
polymorphisms, serum lipids, C-reactive protein, and clinical factors
with incident coronary heart disease (defined as death from or hospitalization
for myocardial infarction, ischemic heart disease, or coronary
intervention) during a median of 4.94 yr follow-up.
Subjects: A predominantly Caucasian general population was
studied.
Results: HDL cholesterol was 0.08 mmol/liter higher in 629A carriers
than in 629CC homozygotes (P 0.001). The unadjusted
coronary hazard was 1.26 [95% confidence interval (CI), 0.95–1.68;
P 0.11] in A carriers compared with CC homozygotes and increased
to 1.46 (95% CI, 1.10–1.95; P 0.01) after adjustment for HDL
cholesterol. This effect remained after additional adjustment for apolipoprotein
A-I, triglycerides, C-reactive protein, age, and gender.
Likewise, the HDL-cholesterol-adjusted hazard ratio was also higher
in AA than in CC homozygotes (hazard ratio, 1.72; 95% CI, 1.22–2.42;
P 0.01). Similar findings were obtained with the TaqIB polymorphism.
The 405V allele was weakly associated with incident coronary
heart disease after HDL cholesterol adjustment (P 0.09).
Conclusions: A common CETP promoter polymorphism, which beneficially
contributes to higher HDL cholesterol, is paradoxically associated
with increased incidence of coronary disease in the general
population. Thus, CETP gene variation may affect coronary risk apart
from the level of HDL cholesterol. (J Clin Endocrinol Metab 91:
3382–3388, 2006) |
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Tags: 2006, An Increased Coronary Risk Is Paradoxically Associated with Common Cholesteryl Ester Transfer Protein Gene Variations That Relate to Higher High-Density Lipoprotein Cholesterol: A Population-Based Stu, None, Scientific Publication
Posted in Scientific publication | Reacties uitgeschakeld
woensdag, december 7th, 2011
| Title | Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity |
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| Year | 2008 |
| Estimated date | 2008-04-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | ABSTRACT
Background: Several findings link systemic lupus
erythematosus (SLE) with C1q, the first molecule of the
classical complement pathway. Polymorphisms of the
C1qA gene are associated with low serum C1q levels in
patients with cutaneous LE, but C1q polymorphisms have
not been studied in patients with systemic lupus.
Objective: To determine whether polymorphisms of the
C1q genes are associated with SLE, disease phenotypes,
serum C1q and CH50 levels.
Methods: DNA for genetic analysis was obtained from
103 Caucasian patients with SLE and their family
members. Five tag single nucleotide polymorphisms (tag
SNPs) served as unique markers for underlying SNPs in
the genes of the C1q protein. The pedigree disequilibrium
test (PDT) was applied to trios to determine association of
markers with SLE, SLE phenotypes, low serum C1q and
low CH50. Single SNP association and haplotype analysis
was also performed.
Results: The PDT revealed a significant association of the
tag SNP rs631090 (covering the C1qB gene) with SLE
(p=0.02). Rs631090 was moderately associated with
low serum C1q levels (p=0.06). In addition, the tag
SNPs rs292001 and rs294183 were associated with more
severe SLE (Systemic Lupus Erythematosus International
Collaborating Clinics (SLICC) damage index score.0;
p=0.007 and p=0.02, respectively). Haplotype analysis
and single SNP association analysis showed no significant
associations, but additional analyses revealed that marker
rs587585 is associated with low serum C1q and CH50
levels.
Conclusions: C1q polymorphisms are associated with
SLE, serum C1q and CH50 levels in a stable founder
population of patients with SLE. Although the studied
population was small and allele frequencies were low, this
is the first study to suggest an association of C1q
polymorphisms with SLE.
Ann Rheum Dis 2009;68:715–720. doi:10.1136/ard.2007.085688 |
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Tags: 2008, Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity, None, Scientific Publication
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woensdag, december 7th, 2011
| Title | Renal Function Dependent Association of AGTR1 Polymorphism (A1166C) and Electrocardiographic Left-Ventricular Hypertrophy |
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| Year | 2007 |
| Estimated date | 2007 |
| Category | Scientific Publication |
| Platform | None |
| Description | Background: The association of renin-angiotensin
system (RAS) polymorphisms and left-ventricular hypertrophy
(LVH) may depend on the presence of risk factors
for LVH, such as renal dysfunction. We studied whether
renal function modulates the association between RAS
polymorphisms and LVH in a cross-sectional study of
8592 inhabitants of Groningen.
Methods: Left-ventricular hypertrophy was determined
with electrocardiograms, using the Cornell voltage-duration
product. The following RAS polymorphisms were determined:
angiotensin II type-1 receptor (AGTR1 A1166C),
angiotensin-converting enzyme (ACE) insertion/deletion (I/
D), and angiotensinogen (AGT G-6A). The AGTR1 A1166C
and ACE I/D polymorphisms were in Hardy-Weinberg equilibrium.
Results: Electrocardiographic LVH was present in 417
(5.0%) subjects. Subjects with LVH were older (53 v 49
years) and overall had more cardiovascular risk factors.
Using logistic regression, creatinine clearance interacted
with the relationship between the AGTR1 A1166C polymorphism
and LVH (, 0.19; P .033). In subjects
with the CC genotype, in contrast to carriers of an A allele,
the prevalence of LVH increased with more pronounced
renal dysfunction. Creatinine clearance also interacted
with the relationship between the ACE I/D polymorphism
and LVH (, 0.12; P .037), although less strongly, and
the other way around. Creatinine clearance did not influence
the association between the AGT G-6A polymorphism
and LVH (, 0.006; P .491).
Conclusions: In this population-based study, the
AGTR1 A1166C polymorphism was associated with
LVH, dependent on concomitant renal dysfunction. A
weaker renal function dependent association between the
ACE I/D polymorphism and LVH was also observed.
Renal function should be taken into account as a relevant
environmental factor for the pathogenetic effects of RAS
polymorphisms. Am J Hypertens 2007;20:1097–1103
© 2007 American Journal of Hypertension, Ltd. |
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Tags: 2007, None, Renal Function Dependent Association of AGTR1 Polymorphism (A1166C) and Electrocardiographic Left-Ventricular Hypertrophy, Scientific Publication
Posted in Scientific publication | Reacties uitgeschakeld
woensdag, december 7th, 2011
| Title | CCR5D32 genotype is associated with outcome in type 2 diabetes mellitus |
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| Year | 2009 |
| Estimated date | 2009-05-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | a b s t r a c t
Aims: To test whether the genetic variant CCR5D32 in the CC-chemokine receptor 5, which
is known to lead to CCR5 deficiency, is associated with mortality in type 2 diabetes patients.
Methods: We examined the effect of presence or absence of the CCR5D32 on overall and
cardiovascular mortality risk in the Zwolle Outpatient Diabetes project Integrating Available
Care (ZODIAC) cohort, a type 2 diabetes patient cohort.
Results: We studied 756 patients with a mean duration of follow-up of 5.4 ( 1.4) years. 194
patients died during follow up of which 83 were cardiovascular deaths. 144 subjects (19%)
carried the CCR5D32 deletion. CCR5D32 carriers had an adjusted hazard ratio of 0.62 (95%CI:
0.40–0.96; p = 0.03) for all-cause mortality and 0.63 (95%CI: 0.33–1.19; p = 0.16) for cardiovascular
mortality.
Conclusions: The presence of CCR5D32 is associated with better survival in type 2 diabetes
patients. These data suggest that it is worthwhile to explore the protective potential of
pharmacological blockade of CCR5 in type 2 diabetic patients
Muntinghe FL, Gross S, Bakker SJ, Landman GW, van der Harst P, Bilo HJ, Navis G, Zuurman MW. CCR5Delta32 genotype is associated with outcome in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2009 Nov;86(2):140-5. Epub 2009 Sep 9. PubMed PMID: 19744740. |
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Tags: 2009, CCR5D32 genotype is associated with outcome in type 2 diabetes mellitus, None, Scientific Publication
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woensdag, december 7th, 2011
| Title | Chemokines in the brain: neuroimmunology and beyond |
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| Year | 2002 |
| Estimated date | 2001-09-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | Chemokines in the brain have been recognised as essential
elements in neurodegenerative diseases and related
neuroinflammation. Recent studies suggest that in addition to the
orchestration of chemotaxis of immune cells, chemokines are also
involved in neurodevelopment and neurophysiological signalling.
Biber K, Zuurman MW, Dijkstra IM, Boddeke HW. Chemokines in the brain: neuroimmunology and beyond. Curr Opin Pharmacol. 2002 Feb;2(1):63-8. Review. PubMed PMID: 11786310. |
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Tags: 2002, Chemokines in the brain: neuroimmunology and beyond, None, Scientific Publication
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