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N Helbecque

Publications and source records attributed to N Helbecque.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intronic polymorphism in the fatty acid transport protein 1 gene is associated with increased plasma triglyceride levels in a French population.

Fatty acids play important biological roles in cells. The precise mechanism whereby fatty acids cross the plasma membrane is still poorly understood. They can cross membranes because of their hydrophobic properties and/or be transported by specific proteins. Recently, a gene coding for fatty acid transport protein 1 (FATP1), an integral plasma membrane protein implicated in this process, was cloned in humans. We screened the gene by single-strand conformation polymorphism analysis and detected an A/G polymorphism in intron 8. We analyzed the potential relations of this genetic polymorphism with various obesity markers and with plasma lipid profiles in a random sample of 1144 French subjects aged 35 to 64 years. We detected statistically significant associations between this FATP1 A/G polymorphism and an increase in plasma triglyceride levels, mainly in women. These results suggest that genetic variability in the FATP1 gene may affect lipid metabolism, especially in women, and reinforce the potential implication of FATP1 in lipid homeostasis.

Adult↗
PubMed1999

Is the LDL receptor-related protein involved in Alzheimer's disease?

LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.

Age of Onset↗
PubMed1998

Dual determination of angiotensin-converting enzyme and angiotensin-II type 1 receptor genotypes as predictors of restenosis after coronary angioplasty.

This study sought to assess the potential influence of the angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1) receptor gene polymorphisms on restenosis after coronary balloon angioplasty. The authors conclude that screening for genetic suspectibility to restenosis based on genotyping of ACE and AT1 receptor polymorphisms before conventional balloon angioplasty is not clinically useful.

Angioplasty, Balloon, Coronary↗
PubMed1998

A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor implicated in adipocyte differentiation, lipid and glucose metabolism. A polymorphism corresponding to a silent C-->T substitution was detected in exon 6 of the PPAR gamma gene. We analysed the relationships between this genetic polymorphism and various markers of the obesity phenotype (body weight, body mass index, waist:hip ratio and plasma leptin levels) in a representative sample of 820 men and women living in northern France. The frequencies of the C and T alleles were 0.860 and 0.140 respectively. In the whole sample no association of the polymorphism with the markers tested was observed but a statistically significant interaction ( P < 0.03) existed between this polymorphism and body mass index for plasma leptin levels. This result suggested that the impact of the PPAR gamma gene polymorphism on plasma leptin levels differed according to the BMI of the subjects. Indeed, obese subjects (BMI >30 kg/m2) bearing at least one T allele ( CT + TT ) had higher plasma leptin levels than subjects who did not (35.0 +/- 17.4 ng/ml versus 28.3 +/- 14.8 ng/ml respectively; P < 0.001). This effect existed in both genders, despite the higher plasma leptin levels observed in women. The plasma leptin level increase was not associated with elevation of body mass index, even though these two variables were highly correlated. Thus for a given leptin level the BMI was relatively lower in obese subjects carrying at least one T allele than in obese CC homozygotes. Our results show that in obese subjects variability within the PPAR gamma gene locus is associated with circulating leptin levels and may modify the relationship between leptin levels and adipose tissue mass.

Adult↗
PubMed1998

The very low density lipoprotein (VLDL) receptor is a genetic susceptibility factor for Alzheimer disease in a European Caucasian population.

The epsilon4 allele of the apolipoprotein E gene (APOE) constitutes a major genetic susceptibility factor for Alzheimer disease (AD). Recently, a polymorphic triplet (CGG) in the very low density lipoprotein receptor (VLDL-R) gene, coding for a receptor binding only apoE-containing lipoproteins, was associated with AD in a Japanese population but not in Caucasian American populations. We explored this association and the potential interaction with the APOE polymorphism in a Caucasian sample of sporadic AD and control subjects of similar ages of European origin. The allelic distribution of the VLDL-R polymorphism differed significantly between Japanese and Caucasian populations (p < 0.0001). However, in our population, the presence of at least one VLDL-R 5 repeat allele increased significantly (p < 0.0003) the probability to develop AD after 65 years of age in APOE epsilon4 allele bearers.

Aged↗
PubMed1997

D allele of the angiotensin I-converting enzyme is a major risk factor for restenosis after coronary stenting.

BACKGROUND: Although intracoronary stent implantation significantly reduces restenosis compared with balloon angioplasty, a minority of patients still develop restenosis predominantly due to neointimal hyperplasia. Experimental studies suggest that the renin-angiotensin system is involved in neointimal hyperplasia after arterial injury. In humans, the plasma and cellular levels of ACE are associated with an I/D genetic polymorphism in the ACE gene, DD patients having higher levels. METHODS AND RESULTS: We investigated a possible relation between the ACE I/D polymorphism and restenosis in 146 patients who underwent successful implantation of a Palmaz-Schatz stent and had 6-month follow-up angiography. The minimal lumen diameter (MLD) before and after the procedure did not differ significantly among the three groups of genotypes (DD, ID, and II). At follow-up, MLD had a significant inverse relationship to the number of D alleles present (DD, 1.65 +/- 0.71 mm; ID, 1.84 +/- 0.60 mm; II, 2.05 +/- 0.61 mm; P < .007). Late luminal loss during the follow-up period was significantly related to the number of D alleles (DD, 0.89 +/- 0.61 mm; ID, 0.60 +/- 0.52 mm; II, 0.40 +/- 0.53 mm; P < .0001). The relative risk of restenosis (defined as a > 50% diameter stenosis at follow-up) approximated by the adjusted odds ratio was 2.00 per number of D alleles (95% confidence interval, 1.03 to 3.88, P < .04). CONCLUSIONS: The ACE I/D polymorphism influences the level of late luminal loss after coronary stent implantation. These results suggest that the renin-angiotensin system may be implicated in the pathogenesis of restenosis after coronary stenting.

Aged↗
PubMed1997

The angiotensin II type 1 receptor gene polymorphism is associated with coronary artery vasoconstriction.

OBJECTIVES: This study sought to assess the potential association of the angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1) receptor gene polymorphisms on coronary vasomotion in humans. BACKGROUND: Abnormal coronary vasomotion plays a role in the clinical expression of coronary atherosclerosis. The components of the renin-angiotensin system are important determinants of vasomotor tone. Furthermore, epidemiologic evidence suggests that these components are involved in the pathogenesis of coronary artery disease. Indeed, two genetic polymorphisms of the ACE and AT1 receptor genes were synergistically associated with the occurrence of myocardial infarction. The influence of these genetic polymorphisms on the risk of myocardial infarction may be related, at least in part, to a deleterious effect on coronary vasomotion. METHODS: We studied the response of angiographically normal human coronary arteries after intravenous injection of methylergonovine maleate, a potent vasoconstrictor whose effects have been previously explored in various aspects of coronary artery disease. We characterized the ACE and AT1 receptor genotypes in a consecutive series of 140 patients with normal coronary arteries. Coronary vasomotion was assessed with quantitative coronary angiography. RESULTS: No effect of the ACE gene polymorphism was detected. Conversely, the patients carrying the AT1 receptor CC genotype (n = 13) had significantly greater vasoconstriction in distal coronary vessels (p < 0.009). CONCLUSIONS: The AT1 receptor gene polymorphism is associated with coronary vasomotion in humans.

Adult↗
PubMed1997

Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.

Angiotensin II↗
PubMed1997

The role of a triplet repeat sequence of the very low density lipoprotein receptor gene in plasma lipid and lipoprotein level variability in humans.

The biological role of the very low density lipoprotein receptor (VLDL-R) in humans is not yet elucidated. This cellular receptor binds apolipoprotein E (apoE)-containing lipoparticles and is mainly expressed in peripheral tissues. The VLDL-R gene contains a polymorphic triplet (CGG) repeat located 19 bp upstream of the initiation codon. We explored the allelic distribution of this repeat in 1384 subjects of European Caucasian origin, 609 of them surviving a myocardial infarction. Six alleles corresponding to 5, 6, 7, 8, 9, and 11 repeats were detected in this population. The alleles 5, 8, and 9 were the most frequent, with frequencies of 0.413, 0.275, and 0.292, respectively. No association was found between the VLDL-R polymorphism and myocardial infarction. In controls without lipid lowering treatment, a statistically significant interaction between VLDL-R genotype and apoE phenotype was found for plasma triglycerides (P < .04), suggesting a gene-gene interaction. There was also a main effect of the VLDL-R polymorphism on LpE:B and LpA-I. The VLDL-R 9 allele was associated with lower levels of plasma LpE:B (P < .05) and higher concentrations of plasma LpA-I (P < .01) than the other alleles. These results suggest that VLDL-R has a modest influence on circulating lipoproteins in humans.

Adult↗
PubMed1996

The deletion allele of the angiotensin I converting enzyme gene as a genetic susceptibility factor for cognitive impairment.

Experimental evidences suggest an implication of the renin angiotensin system (RAS) as a potential determinant of cognitive functions. To explore this hypothesis, we compared the distribution of an insertion (I)/deletion (D) polymorphism of the gene coding for the angiotensin I converting enzyme (ACE), a key enzyme of the RAS, in 228 elderly with cognitive impairment to that of 255 controls. The ACE D allele frequency was higher in the group with cognitive impairment (0.594) than in controls (0.514) (P < 0.02). The ACE DD genotype carriers had an increased risk of cognitive impairment (OR = 1.60, 95% CI (1.04-2.36), P < 0.03), independent of other risk factors of cognitive impairment: age, gender and presence of the apolipoprotein E epsilon 4 allele. This association was stronger in men (OR = 3.25, 95% CI (1.40-7.58), P < 0.006). This result suggests a possible implication of the RAS in human brain and cognitive functions.

Aged↗
PubMed1995

Relation between the deletion polymorphism of the angiotensin-converting enzyme gene and late luminal narrowing after coronary angioplasty.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been implicated in the pathogenesis of coronary artery disease. The deletion allele is strongly associated with the level of circulating ACE and is a potent risk factor for myocardial infarction. Recently, the deletion allele was also associated with the occurrence of visually diagnosed restenosis after percutaneous transluminal coronary angioplasty (PTCA) in a selected population of patients with acute myocardial infarction. METHODS AND RESULTS: We investigated the influence of the ACE I/D polymorphism on the occurrence of restenosis after PTCA with the use of quantitative coronary angiography. ACE I/D genotypes were characterized in 118 consecutive patients who had one-vessel disease and were undergoing systematic angiographic follow-up. Coronary angiograms were analyzed before and after PTCA and at follow-up (7.4 +/- 3.0 months). Before PTCA, there were no clinical or angiographic differences among the three groups of genotypes (DD, n = 39; ID, n = 62; II, n = 17). After PTCA, the mean differences in minimal luminal diameter between post-PTCA and pre-PTCA angiograms (acute gain) were identical in the three groups, as was the mean percent residual stenosis. At follow-up angiography, the mean difference in minimal coronary luminal diameter between post-PTCA and follow-up angiograms (late loss) was not significantly different in the three groups of genotypes. The percentage of patients with restenosis defined as a > 50% stenosis was identical in the three groups. CONCLUSIONS: In this quantitative study, the I/D polymorphism of the ACE gene had no influence on the occurrence of restenosis after coronary angioplasty.

Adult↗
PubMed1995

Influence of the methyl substituents of a thiazole-containing lexitropsin on the mode of binding to DNA.

We have studied the DNA-binding properties of two thiazole-containing analogues of netropsin which differ by the absence (Thia-Nt) or presence (Methia-Nt) of methyl groups on the thiazole rings. The mode of binding to DNA of the two lexitropsins was investigated by circular dichroism, electric linear dichroism and viscosity measurements. The spectroscopic and hydrodynamic results indicate that the non-methylated lexitropsin binds to the minor groove of DNA, whereas the methylated analogue behaves as an intercalator. Our findings led to the notion that the methyl substituents on the thiazole rings might play a significant part in the intercalation process.

Animals↗
PubMed1993

Synthesis and antitumor properties of an anthraquinone bisubstituted by the copper chelating peptide Gly-Gly-L-His.

A new molecule 4 [(GGH-DAE)2DHQ] associating the 1,4,5,8-tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose.

Animals↗
PubMed1993

Cyclomaltodextrin glucanotransferase from Bacillus circulans E 192: nitration with tetranitromethane.

Nitration of tyrosine residues was performed on Bacillus circulans E 192 cyclomaltodextrin glucanotransferase (CGTase) using tetranitromethane (TNM). A maximum of 15 out of 28 tyrosine residues is modified with 8 mM TNM, entailing a concomitant loss of enzymic activity and tryptophan fluorescence. Spectroscopic studies suggest that these two phenomena are related to an impairment of the enzyme conformation as a consequence of the tyrosine nitration. The presence of 5 mM acarbose during the CGTase nitration results in the protection of one tyrosine residue and the rate of inactivation is reduced 9.4-fold. These results support a contribution of a tyrosine residue in the CGTase catalytic site. The nitration of CGTase also entails a decrease in the enzyme's affinity for a beta-cyclodextrin (beta-CD) co-polymer. Kinetic and analytical investigations on isolated modified enzymes support the concept that this phenomenon is unrelated to the modification of tyrosine residues, but rather concerns a side reaction of the reagent occurring at the raw-starch-binding site of the CGTase.

Acarbose↗
PubMed1992

The coordination of copper(II) to 1-hydroxy-4-(glycyl-histidyl-lysine)-anthraquinone; a synthetic model of anthraquinone anti-cancer drugs.

Results are reported of a pH-metric and spectroscopic (CD and ESR) study of the complexes formed between the pseudo-peptide 1-hydroxy-4-(Gly-His-Lys)-anthraquinone (Q-GHK) since, when complexed to copper ions, Q-GHK has been shown to be very effective in promoting the formation of free radicals and inducing DNA cleavage. Q-GHK forms very stable complexes with copper, the major species being bonded to three nitrogen donors in the coordination plane: an imidazole-N of the His residue and the peptide nitrogens of the Gly and His residues. This species is probably stabilized through bonding of the fourth planar coordination site of Cu(II) to the 9-anthraquinone oxygen. At high Q-GHK:copper ratios a second Q-GHK molecule is coordinated through its imidazole-N donor.

Anthraquinones↗