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Biomedical subjects

R Gueguen

Publications and source records attributed to R Gueguen.

At least 37 records · Page 2Linked to original sources

DNA polymorphisms of human apolipoprotein A-IV gene: frequency and effects on lipid, lipoprotein and apolipoprotein levels in a French population.

Genetic polymorphisms of apolipoprotein (apo) A-IV have been shown to influence lipoprotein metabolism in some human populations. In this study, we have evaluated the physiological effect of three apo A-IV polymorphisms (Gln360- > His, Thr347- > Ser and XbaI within the second intron of the apo A-IV gene), in a French population, on seven quantitative traits: total cholesterol and triglycerides, cholesterol of HDL, apo A-IV, apo B, apo A-I and glucose. The polymorphism at amino-acid 360 was determined by direct analysis of polymerase chain reaction products. The allele frequencies were 0.92 for the A-IV1 and 0.08 for the A-IV2 allele. The genetic polymorphism at codon 347 was investigated by allele-specific oligonucleotide hybridization. The allele frequencies of the two alleles, A-IV347Thr and A-IV347Ser, were 0.78 and 0.22, respectively. The XbaI polymorphism was investigated by polymerase chain reaction followed by XbaI restriction enzyme digestion of the amplified products. The frequencies of the two apo A-IV alleles, XbaI-1 and XbaI-2, were 0.79 and 0.21, respectively. None of the three apo A-IV polymorphisms had a significant effect on lipoprotein, apolipoprotein and glucose levels.

Adult↗

Acetylation phenotypes and biological variation in a French Caucasian population.

Factors affecting the caffeine acetylation phenotype were investigated in a French Caucasian population of 150 unrelated supposedly healthy subjects, aged 18 to 63 years. This population, including 75 men and 75 women, was used to determine whether the acetylation polymorphism is related to environmental influences such as smoking habits, intake of alcohol, use of oral contraceptives, use of certain drugs. The acetylation phenotype was assessed from the molar ratio of two caffeine metabolites: 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine. For values less than 0.85, the subjects were classified as poor acetylators (frequency, mean +/- SD: 61.3 +/- 7.9%) in this study. Dose recoveries of 5-acetylamino-6-formylamino-3-methyluracil (mean +/- SD) were 1.26 +/- 0.85% and 3.58 +/- 1.64% in slow and rapid acetylators, respectively. The recovery (mean +/- SD) of 1-methylxanthine in the 3 hour-urine was 2.86 +/- 1.51% in slow acetylators and 2.36 +/- 1.27% in rapid acetylators. The mean value (and SD) of the molar ratio was 0.437 (0.177) and 1.669 (0.651) for slow and rapid acetylators. Three other metabolite ratios can also provide an acetylation index: 5-acetylamino-6-formylamino-3-methyluracil/5-acetylamino-6-formylamino-3 - methyluracil + 1-methylxanthine + 1-methyluric acid; 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid; and 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid + 1,7-dimethylxanthine with a bimodal distribution for the former and a trimodal distribution for the two latter ratios, both showing about 95% concordance with the 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine ratio. Age did not influence the excretion of caffeine and its five major metabolites. A marked influence of sex was observed only on the unchanged caffeine excretion, and the effect was greater in slow acetylators than in rapid acetylators. The 5-acetylamino-6-formylamino-3-methyluracil excretion was about three times higher in rapid acetylators than in slow acetylators in both sexes.

Acetylation↗

The role of genetics in defining reference values and health status.

Since its establishment, the Center for Preventive Medicine in Vandoeuvre-les-Nancy, France, performed specific studies on healthy humans, and its approach was very useful for defining reference values. Prevention should extend its interest to chronic diseases. The majority of important adult disorders are partially genetically determined. Genetic markers are also useful as exclusion or as partition criteria in the production of reference values. Results are presented that were obtained for apolipoproteins E, B and AIV, frequencies of these polymorphisms in the Lorraine population, and relationships between these polymorphisms and lipid metabolism-related parameters. Health checkup centers, in particular those involved in family screening, are well suited for resembling many data concerning environmental factors: tobacco consumption, alimentation habits, or alcohol and drug consumption. Simultaneous determination of genetic markers could allow the determination of an individual's susceptibility or resistance to developing a disease and to prepare a preventive action.

Environmental Exposure↗

Determinants of hormonal replacement therapy in recently postmenopausal women.

Although the efficacy of hormonal replacement therapy (HRT) on the consequences of the menopause is not questioned, it appears that in Europe and in the USA only a small proportion of women are users of HRT. In this study, we examined the prevalence and the determinants of HRT among 1986 French menopausal women, aged 45 to 55 years, presenting to a preventive medicine centre. Overall, 8.1% of women reported current use of HRT. The estrogen preparation most commonly reported was transcutaneous 17 beta-oestradiol. The first determinant of current HRT was birth-place. Women born in France were nearly four times more likely to be on treatment than foreign-born women. A surgical menopause multiplied the probability of current HRT by 2, as did a high level of education. An age at first pregnancy of more than 20 and less than 4 children were also positively linked with HRT use. Even in this population of recently menopausal women, volunteering to undergo health evaluation, the prevalence of HRT was low. The reservations towards HRT may be partly due to the women themselves, and partly due to the physicians. It seems very important to inform the medical profession about the risks and benefits of HRT, and to understand more precisely the reasons why so few women use HRT.

Administration, Cutaneous↗

Multivariate genetic analysis of high density lipoprotein particles.

The aim of this study was to investigate the effect of genetic factors on three components of plasma high density lipoproteins, HDL-cholesterol (HDL-C), apolipoprotein A-I (apo A-I) and lipoprotein particle Lp A-I (Lp A-I), which contains apo A-I but not apo A-II. These analyses were carried out on 106 nuclear families with one or more children (407 subjects) who volunteered for health screening at the Center for Preventive Medicine, Vandoeuvre, France. After adjustment by stepwise multiple linear regression analysis for age, gender, weight, height, ponderosity, alcohol consumption, smoking habits, and hormonal treatment in females, a multifactorial model (considering the effect of polygenes, individual, specific, environmental and common household factors) was fitted to each variable separately. The hypothesis of no common household effects was accepted for each of the traits. The contribution of genetic factors to inter-individual variance was larger than the contribution of environmental factors for apo A-I (h2 = 0.81) and Lp A-I (h2 = 0.63) but not for HDL-C (h2 = 0.44). Bivariate analyses were carried out by parameterizing covariance components between traits. The genetic correlations were always significantly different from zero. They were estimated to be 0.73 between HDL-C and apo A-I, 0.40 between HDL-C and Lp A-I, 0.51 between apo A-I and Lp A-I. These results suggest that HDL-C, apo A-I and Lp A-I are only in part affected by the same genes and that the measurement of lipids as well as the apo A-I and Lp A-I gives complementary and different information on the metabolic and genetic aspects.

Adolescent↗

Reference limits of plasma fibrinogen.

Fibrinogen is considered to be a strong predictor and independent factor of cardiovascular diseases. The data presented here describe the baseline measurements of fibrinogen in 1008 apparently healthy subjects, aged 4-60 years and their relationship to age, sex, body weight, smoking, alcohol, and use of oral contraceptives. Pearson's correlations and a linear multiple regression model were used. Plasma fibrinogen was measured kinetically in a photometer, the Behring Chromotimer, using the CTS-fibrinogen method. There were neither statistical difference between girls and boys aged 4-20 years nor correlation with variables related to cardiovascular diseases. In adults, we found an increase of plasma fibrinogen concentration with age and no statistical difference between men and women, except in subjects aged 40-50 years. There was a positive correlation between fibrinogen and ponderal index. In women aged 20-30, 30-40, 40-50 and 50-60 years, the mean fibrinogen concentrations increased of 0.009, 0.021, 0.010 and 0.015 g/l for one percent of overweight, in each subgroup respectively. In women aged 20-30 years using oral contraceptives, the mean fibrinogen concentration was 0.19 g/l higher than in women not using oral contraceptives. The smoking effect was observed only in 30-40 year-old men. Each cigarette smoked per day increases of the mean fibrinogen by 0.35 g/l after standardization for ponderal index and alcohol consumption. Alcohol consumption was negatively correlated to plasma fibrinogen in subjects 30-40 years old. In women, 1 g of alcohol per day induces a 0.008 g/l decrease in the mean fibrinogen while in men the decrease is 0.004 g/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Population genetics of hypervariable loci: analysis of PCR based VNTR polymorphism within a population.

Using a polymerase chain reaction (PCR) based method, genotypes at two hypervariable loci (3' to the Apo-B-structural gene and at the ApoC-II gene) were determined by size classification of alleles. Genotype data at the Apo-B locus (Apo-B VNTR) were obtained on 240 French Caucasians; the sample size for the ApoC-II VNTR was 162. For 160 individuals two-locus genotype data were available. Applications of some recently developed statistical methods to these data indicate that both of these loci are at Hardy-Weinberg equilibrium (HWE) and there is no indication of allelic associations between these two unlinked loci. In addition, the observed numbers of alleles (12 for the Apo-B and 11 for the ApoC-II VNTR loci) are also consistent with their respective expectations based on the observed heterozygosities (76.9% for the Apo-B and 85.9% for the ApoC-II loci) suggesting genetic homogeneity of this population-based sample. The multimodal distribution of allele sizes observed for both loci indicate that the production of new alleles at such VNTR loci may be caused by more than one molecular mechanism. The utility of such highly polymorphic loci for human genetic research and forensic applications are discussed in the context of these findings.

Alleles↗

[The status of blood pressure over a 10-year period].

The aim of this study is to relate the evolution of blood pressure (BP) measured every 5 years during 10 years in 12,824 healthy adults and children from both sexes. At the first evaluation, 2,856 were 4-15 years of age, 1,471 were 15-25, 6,590 were 25-45 and 1,907 were 45-65. The result of BP were adjusted according to possible effects of age, height or year of examination. Correlation coefficients at 5 and 10 years for the male patients are 0.38 and 0.34 (systolic BP and 0.23 and 0.18 (diastolic BP); for the female patients they are 0.36 and 0.31 (systolic BP) and 0.23 and 0.17 (diastolic BP). The reliability of the correlations increases according to age at first examination: for an initial age between 4 and 10 years, the correlation coefficient between first and last evaluation is 0.14 while for an initial age of 45-65 years it is 0.38 (systolic BP). The predictive value of a relatively high BP defined as percentage of patients whose systolic BP is staying in the upper fifth of the BP distribution ten years later is for increasing age group: 28.7%, 31.1%, 39.7%, 42.5%; that means a relative risk moving from 1.34 to 3.17. Sensitivity of detection of male patients whose systolic BP will be in the upper fifth of the distribution varies from 22 to 42% according to age, with a specificity of 86.3 to 82.2%. The results are sensibly similar in the female patients and for diastolic BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Frequency and effects of the apolipoprotein A-IV polymorphism.

Plasma from 158 presumed healthy nuclear families has been analyzed by high-resolution, two-dimensional electrophoresis to study the frequency and effects of the genetic polymorphism in human apolipoprotein A-IV. Two common alleles, apo A-IV 1 and apo A-IV 2 were detected with relative frequencies of 0.943 and 0.057, respectively. Autosomal codominant transmission of these two alleles coded for by a single structural locus was demonstrated. Furthermore, we studied the effects of this apo A-IV variability on total plasma cholesterol, triglyceride, glucose levels and gamma-glutamyltransferase activity. Statistically significant differences among apo A-IV genotypes for the average glucose level were detected. The average effect of the apo A-IV 1 allele was to lower plasma glucose levels by 0.013 mmol/l, whereas the average effect of the apo A-IV 2 allele was to raise glucose levels by 0.213 mmol/l.

Adult↗

[Blood pressure variations from clinostatism to orthostatism].

The reactivity of blood pressure (BP) and heart rate (HR) to change from supine to standing position was examined in 257 healthy adults, adolescents and children divided into equivalent group of both sexes. BP and HR were measured every minute during 14 minutes in a supine position then during 5 minutes in a standing position with an automatic device using the oscillometry method. A second measurement session was repeated two weeks later. On most patients an increase of diastolic BP (7.73 +/- 4.34 mmHg) and HR (16.40 +/- 7.47/mn) was observed after standing whereas systolic BP modifications were inconstant (2.19 +/- 5.55 mmHg). A comparison of variability indices according to postural state showed a significant higher variability index in a standing position only in female subjects. There was no difference according to age groups. Reproducibility of diastolic BP and HR increase is good two weeks later in respectively 65 p. 100 and 80 p. 100 subjects but it appears very poor for systolic BP. The results in healthy subjects would be compared to those observed in hypertensives to determinate if a postural change test may provide a clinical simple way to discriminate abnormalities in blood pressure regulation.

Adolescent↗

[Evaluation of short stature in boys: delayed growth or constitutional short size?].

When assessing a child with short stature it may be difficult to differentiate between delayed growth and adolescence and constitutional short stature, which usually provide a completely different prognosis of adult height. The growth data on 43 boys were retrospectively studied after they had reached adult height. Two groups were differentiated according to their final height, i.e. boys with delayed growth and adolescence; and boys with constitutional short stature. From these data a discriminant analysis was worked out that could be used as a means to facilitate the prediction of adult height in boys short stature.

Age Determination by Skeleton↗

An analysis of genotype effects and their interactions by using the apolipoprotein E polymorphism and longitudinal data.

We investigate the interaction between the apolipoprotein E polymorphism and changes in weight and height as they affect the longitudinal profile of total cholesterol, triglyceride, beta lipoprotein, and glucose levels. Data were available on a sample of 466 individuals in 158 nuclear families from Nancy, France. Longitudinal data analyses were carried out on 128 unrelated adults and 56 unrelated children. We estimate the relative frequencies of the epsilon 2, epsilon 3, and epsilon 4 apolipoprotein E alleles in this population to be .120, .764, and .116, respectively. There is no significant evidence from these data that supports an effect of the apolipoprotein E polymorphism on the longitudinal profile of any of the variables considered. There is a significant interaction between the effects of this gene and weight change on the longitudinal change of serum triglyceride and beta lipoprotein levels in adults. In conjunction with weight gain, individuals with an epsilon 4 allele are expected to show a larger increase in triglyceride levels (0.15 +/- 0.03 mmol/L/kg) compared with individuals with no epsilon 4 allele. An increased production of very-low-density lipoprotein (VLDL) as one gains weight, along with retarded VLDL clearance attributable to the effects of the epsilon 4 allele, may account for this results. The significant interaction between the apolipoprotein E polymorphism and changes in weight on the longitudinal change in triglyceride levels corroborates epidemiological studies reporting that the epsilon 4 allele increases the risk of hypertriglyceridemia among obese individuals.

Apolipoproteins E↗

Alanine aminopeptidase in serum: biological variations and reference limits.

We studied the effect of various factors on the biological variation of alanine aminopeptidase (AAP, EC 3.4.11.2) in serum in a population of 2178 apparently healthy subjects and in subjects taking specific drugs. To measure AAP, we used an automated assay, with alanyl-4-nitroanilide as substrate. AAP activity concentrations were significantly higher in males than in females in all age groups between 10 and 55 years. The highest mean AAP values were found for children between 10 and 14 years. In male heavy smokers, AAP values were 8% higher than in moderate or nonsmokers (P less than 0.001); in females, this effect was less pronounced. AAP concentrations were higher in subjects consuming over 44 g of ethanol a day than in those consuming less (P less than 0.01 for men, P less than 0.05 for women). The use of oral contraceptives increased AAP values by 12% (P less than 0.001). Hypolipidemic drugs caused lower values for AAP in men (P less than 0.001). Subjects showing induction of gamma-glutamyltransferase (EC 2.3.2.2) by anticonvulsant drugs had also higher AAP activities (by 23%). Taking these data into account, we established reference limits for AAP in serum.

Adolescent↗

[Measurement of arterial pressure by an automatic method. Comparison of various devices for automatic measurement].

A comparative study of three Dinamap 845 instruments was carried out in order to find out whether the use of several automated blood pressure recorders constitutes a major source of variations in epidemiological studies. The three instruments were compared by means of a variant analysis model and proved to have virtually the same accuracy. Only one of them gave a slightly different diastolic pressure reading. No matter how useful are instruments for automated blood pressure measurement, comparisons between several recorders of the same type and regular testing for accuracy seem to be necessary in epidemiological studies.

Analysis of Variance↗