Search

International audience; BACKGROUND:We have investigated the association between 4 cis- and trans-genetic variants (rs6921438, rs4416670, rs6993770 and rs10738760) of the vascular endothelial growth factor (VEGF) gene and metabolic syndrome (MetS) and its individual components in an Iranian population.MATERIAL & METHOD:Three hundred and thirty-six subjects were enrolled and MetS was defined according to the International-Diabetes-Federation (IDF) criteria. Genotyping was carried out in all the individuals for 4 VEGF genetic variants using an assay based on a combination of multiplex polymerase chain reaction and biochip array hybridization.RESULTS:As may be expected, patients with MetS had significantly higher levels of serum high-sensitivity C-reactive protein, waist circumference, hip circumference, body mass index, fat percentage, systolic blood pressure, diastolic blood pressure and triglyceride, whereas the high-density lipoprotein cholesterol levels were significantly lower, compared to the control group (P < 0.05). We also found that 1 of the VEGF- level associated genetic variants, rs6993770, was associated with the presence of MetS; the less common T allele at this locus was associated with an increased risk for MetS. This association remained significant after adjustment for confounding factors (P = 0.007). Individuals with MetS carrying the AT + TT genotypes had markedly higher levels of fasting blood glucose, triglyceride and systolic blood pressure (P < 0.05).CONCLUSIONS:We have found an association between the rs6993770 polymorphism and MetS. This gene variant was also associated with serum VEGF concentrations. There was also an association between this variant and the individual components of the MetS, including triglyceride, fasting blood glucose and systolic blood pressure.Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

The aim of this study was to investigate the difference in the prevalence of metabolic syndrome and its components between an Iranian and a French population.The prevalence of metabolic syndrome, defined according to the Adult Treatment Panel III (ATP III), and of related abnormalities, was estimated in 1,386 French and 1,194 Iranian adults.The prevalence of metabolic syndrome was significantly higher in Iranian women (55.0%), followed by Iranian men (30.1%), than in French men (13.7%) and French women (6.6%). Iranian women were characterized by high rates of abdominal obesity (65.0%), hypertension (52.1%), hypertriglyceridemia (43.1%), and low high-density lipoprotein cholesterol (HDL-C; 92.7%). Iranian men were characterized by high rates of hypertension (48.9%), hypertriglyceridemia (42.8%), and low HDL-C (81.8%). French men had high rates of hypertension (44.7%) and mild rates of hypertriglyceridemia (28.6%) and hyperglycemia (23.9%). There was a relationship between waist circumference and the lipid components of metabolic syndrome in both countries.The main finding of this study is the high prevalence of low HDL-C concentrations in the Iranian population, especially in Iranian women, compared with French women. Explanation of this observation could help in establishing prevention strategies.

Background We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. Methods At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. Results At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters “risk lipids” and “protective lipids”. Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: “liver enzymes”, “adiposity/blood pressure” and “inflammation”. Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. Conclusions In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits.

Serum leptin has been reported to be associated in a sex-dependent manner with C-reactive protein (CRP), independently of adiposity. We tested the hypothesis that leptin is associated, independently of anthropometry indexes and in a sex-dependent way, with other inflammatory markers and variables related to metabolic syndrome (MS). In 384 healthy middle-aged adults (192 men and 192 women) total fat mass (FM), waist circumference (WC), serum leptin and 15 MS-related parameters (systolic and diastolic blood pressure, triglycerides, cholesterol, high density lipoprotein (HDL)-cholesterol, apo AI and B, fasting glucose, uric acid, CRP, orosomucoid and haptoglobin levels and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities) were measured. After adjustment for age, alcohol and cigarette consumption, WC, and total FM, leptin concentration was significantly associated with serum triglycerides, total cholesterol, apo B, uric acid and haptoglobin concentrations and liver enzyme activity only in men, and with apo AI, HDL-cholesterol (only borderline) and CRP only in women. Sex interaction terms were significant for total cholesterol, apo B, HDL cholesterol, uric acid, ALAT and GGT, and borderline significant for triglycerides, apo AI and ASAT. In this healthy population, leptin is significantly associated with various MS factors, independently of WC and total FM, depending on gender. Our study provides further evidence of sex-related differences mediated by leptin in inflammatory mechanisms and other MS-related metabolic pathways.

Aims: The human formyl peptide receptor (FPR) is a G protein-coupled chemoattractant receptor that is thought to mediate inflammatory responses. The FPR1 gene is highly polymorphic. In a recent study, the FPR1 c.32C>T SNP, resulting in the amino-acid substitution I11T, was reported to be significantly associated with C-reactive protein levels. Therefore, this study sought to determine if the impact of such a genetic variation extends to other clinical parameters associated with inflammation, including cytokines, adhesion molecules and inflammatory markers. Materials & methods: This study was carried out on a subsample of 325 adults selected from the STANISLAS cohort study. The FPR1 c.32C>T SNP was genotyped using PCR amplification followed by restriction enzyme digestion. Anthropometric measurements and biochemical profiles were assessed for each individual. Results: The allele frequencies of FPR1 c.32C>T were 0.74 for the 32C allele and 0.26 for the 32T allele. Genotype frequencies were 0.55 for C/C, 0.38 for C/T and 0.07 for T/T. After adjusting for age, sex, BMI, alcohol and cigarette consumption, oral contraceptive, antibiotics and anti-inflammatory drug use, statistical analysis (under a recessive model of inheritance) demonstrated that serum E-selectin levels were 68% lower in individuals homozygous for T/T than in those with C/T or C/C genotypes (p = 0.001). However, no significant correlations were found for C-reactive protein or the other 18 tested clinical parameters that were analyzed in this study. Conclusion: The FPR1 c.32C>T SNP may be associated with E-selectin levels in the French population. Although of importance, these findings need confirmation in larger studies.

The purpose of the present longitudinal study was to describe the associations between the 5-year changes in body mass index (BMI) and alterations in the clusters of metabolic syndrome (MS)-related factors.The study population comprised 1099 middle-aged adults drawn from the Stanislas study. Individuals were stratified into four groups according to the 5-year changes in BMI (weight loss (0 kg/m(2)), and weight gain (0-1, 1-2 and2 kg/m(2))). Changes in various MS-related variables and clusters were compared between groups: anthropometric indices, blood pressure, lipid and inflammatory markers, liver enzymes, uric acid and the five summary factors extracted by using factor analysis ('risk lipids', 'liver enzymes', 'inflammation', 'protective lipids' and 'blood pressure').There was a strong linear trend between increasing BMI and worsening of risk lipids and blood pressure factors for both men and women (Por=0.001). In men only, liver enzymes and protective lipids factors were significantly related to the 5-year gain of BMI (Por=0.001), whereas inflammation factor positively increased across the four BMI-change groups, in women only. Interaction terms for sex were statistically significant for inflammation and liver enzymes clusters.In our population, there was a strong linear trend between increasing BMI and worsening of various MS-related variables. More interestingly, the identification of five factors associated with BMI changes dependent to gender, support the hypothesis that weight gain, and probably obesity, trigger metabolic mechanisms that differ between men and women.

Neural tube defects (NTDs) are severe congenital malformations due to failure of neural tube formation in early pregnancy. The proof that folic acid prevents NTDs raises the question of whether other parts of homocysteine (Hcy) metabolism may affect rates of NTDs. This French case-control study covered: 77 women aged 17–42 years sampled prior to elective abortion for a severe NTDs (cases) and 61 women aged 20–43 years with a normal pregnancy. Plasma and erythrocyte folate, plasma B6, B12 and Hcy were tested as five polymorphisms MTHFR 677 C T, MTHFR 1298 A C, MTR 2756 A G, MTTR 66 A G and TCN2 776 C G. Cases had significantly lower erythrocyte folate, plasma folate, B12 and B6 concentrations than the controls, and higher Hcy concentration. The odds ratio was 2.15 (95% CI: 1.00–4.59) for women with the MTRR 66 A G allele and it was decreased for mothers carrying the MTHFR 1298 A C allele. In multivariate analysis, only the erythrocyte folate concentration (P = 0.005) and plasma B6 concentration (P = 0.020) were predictors. Red cell folate is the main determinant of NTDs in France. Folic acid supplement or flour fortification would prevent most cases. Increased consumption of vitamins B12 and B6 could contribute to the prevention of NTDs. Genetic polymorphisms played only a small role. Until folic acid fortification becomes mandatory, all women of reproductive age should consume folic acid in a multivitamin that also contains B12 and B6. © 2008 Wiley-Liss, Inc.

We aimed at estimating additive genetic heritability, household component effect and the influence of common alleles of the apolipoprotein E gene (APOE) on serum high-sensitivity C-reactive protein (hs-CRP) concentrations and the subsequent changes over 5 years. A sub-sample of 320 nuclear families was randomly selected from the Stanislas Family Study. Serum hs-CRP concentration was measured by immunonephelometry at entrance and after 5 years. APOE alleles were determined by restriction fragment length polymorphism. After adjustment for covariates, the number of the epsilon4 allele was negatively associated with serum concentration of hs-CRP in the whole sample, at entrance and 5 years later, without significant interaction with sex by generation groups (P=0.003 and P=0.0003, respectively). However, no significant association was found between epsilon4 allele and 5-year changes in hs-CRP concentration. Using a variance component analysis, no significant genetic influence was shown in family aggregation of both hs-CRP measurements and 5-year changes; the household common component was between 6.5 and 12.8%. In addition, after adjustment for APOE gene polymorphisms, degrees of resemblance were almost unchanged. In the Stanislas Family Study, epsilon4 allele of the APOE gene was associated with lower hs-CRP concentration, but not with 5-year changes. However, variance component analysis did not evidence a significant polygenic effect.

In the area of proteomic, results of analysis were for a long time dependant on analytical variations. Nowadays, due to the emergence of new technologies and controls of data, these variations are less important than those due to preanalytical conditions, which are difficult to overcome. The reasons are due to the number of parameters and to the fact that the biologist is not always fully informed. In this document, we present the main preanalytical factors of variation, and their effects on the results of analysis. New technologies involving mass spectrometry are very promising, but they are very sensitive to parameters like the stability of samples and the choice of the clotting agent. Thus, it is more and more necessary to take these data into account.

Background: A 776C>G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B12. Objective: To evaluate the world-wide prevalence of this variant and its association with homocysteine plasma level. Methods: The study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and in 251 Afro-Africans subjects with severe malaria. Results: The frequencies of 776G allele were the highest in China (0.607 [95% confidence interval:0.554-0.659]), low in West Africa (Benin and Togo, 0.178 [0.154-0.206]) and intermediate in France (0.445 [0.408-0.481]), Italy (0.352 [0.299-0.409]), Marocco (0.370 [0.300-0.447]) and Mexico (0.374 [0.392-0.41.9]). The 776GG genotype was more frequent in Afro-Americans from New York (16.7 [8.4-30.7]) and in Afro-African patients with severe malaria (6.0% [95%CI: 3.7-9.6]) than in healthy Afro-African volunteers (p=0.0004 and p=0.0329, respectively), while no difference was observed for MTHFR 677TT and 677T allele. A disequilibrium of TCN2 genotype distribution was recorded in the patients with severe malaria, with a 2-fold higher GG genotypes than expected (p=0.010). An association between the TCN2 polymorphism and homocysteine was observed only in Mexico and France, the two countries with the highest rate of low plasma concentration of vitamin B12 (

Aim: To investigate whether the interactions of CYP2C19*2 and CYP2C19*17 with smoking are associated with the levels of P2Y12 receptor inhibition and CRP, in on-thienopyridine post-stenting patients. Methods & results: At 1-month follow-up, the interactions of smoking and CYP2C19 polymorphisms on the vasodilator-stimulated phosphoprotein – platelet reactivity index (VASP PRI), and CRP were explored in three metabolizing groups (1128 patients) as follow: poor metabolizers (*2 carriers/*17 noncarriers); intermediate metabolizers (*2 carriers/*17 carriers or *2 noncarriers/*17 noncarriers); and ultrarapidmetabolizers (*2 allele noncarriers/*17 carriers). The interactions of metabolizing status and smoking was significant for CRP (p = 0.001) but not for VASP PRI (p = 0.734). Conclusion: Interaction between CYP2C19 polymorphisms and smoking modifies on-treatment CRP level of post-stenting, on-thienopyridine patients. This effect seems to be independent to the level of P2Y12 receptor inhibition. Original submitted 1 August 2014; Revision submitted 4 February 2015

Background: Methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism is heterogeneously distributed worldwide, with the highest and lowest frequencies of the T allele in Mexico and Africa, respectively, and a south-to-north gradient in Europe. Distribution of MTHFR 1298A→C is less well known. It has been hypothesized that 677T frequency could result in part from gene-nutrient interactions. Objective: The objective was to compare the association of 677T and 1298C alleles with plasma concentrations of homocysteine, folate, and vitamin B-12 in geographical areas with contrasting 677T allele frequencies. Design: Healthy young adults (n = 1:277) were recruited in Mexico City, the West African countries of Benin and Togo, France, and Sicily (Italy). Homocysteine, folate, and vitamin B-12 were measured in plasma, and MTHFR polymorphisms were measured in genomic DNA. Results: Mexico City and Sicily reported the highest and Benin and Togo reported the lowest plasma concentrations of folate. Mexico City had the highest 677T allele prevalence and the lowest influence of 677TT genotype on homocysteine, whereas the opposite was observed in Africa. The prevalence of the 1298C allele was lowest in the Mexicans and Africans and highest in the French. The percentage of the 677T genotype was significantly associated with the folate concentrations in 677CC carriers in a u nivariate analysis (R = 0.976; 95% CI: 0.797, 0.996; P < 0.0002) and in a multiple regression model that included homocysteine, vitamin B-12, and age (P = 0.0002). Conclusion: Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677C→T polymorphism and folate status that may confer a selective advantage of TT-homozygous genotype when dietary intake of folate is adequate, at least in the areas studied.

The cause of the non-disjunction leading to trisomy 21 remains unclear. Recent evidence has suggested that 5, 10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21. The purpose of the present study was to analyse these findings among the French population and to investigate whether common polymorphisms in genes of the folate and homocysteine pathway, including the MTHFR 677C>T, MTHFR 1298A>C, the methionine synthase (MTR) 2756A>G, the cystathionine β-synthase (CBS) 844Ins68 and the reduced folate carrier (RFC-1) 80G>A polymorphisms, contribute to the risk of trisomy 21. The risk was studied by analysing independent and combined genotypes in 119 case mothers and 119 control mothers. The MTHFR 677T, MTHFR 1298C, MTR2756G, MTRR66G, CBSIns68+ and the RFC-1 80G allele frequencies were not significantly different among French case mothers, compared with control mothers. The risk of having a child with trisomy 21 did not appear to be linked to polymorphisms in genes associated with folate and homocysteine metabolism.

Background Although numerous environmental factors are documented to influence serum retinol and alpha-tocopherol concentrations, little is known about the genetic versus the environmental contributions to variations in these traits. Objective The aim of this study was to estimate additive genetic heritability and household effects for serum retinol and alpha-tocopherol concentrations in a variance component analysis. Design In a sample of 387 French families, information on serum retinol and alpha-tocopherol concentrations, usual dietary intake, lifestyle, and serum lipid profiles and related polymorphisms (apolipoprotein E, apolipoprotein C-III, apolipoprotein B, cholesteryl ester transfer protein, and lipoprotein lipase) was obtained. Results For serum retinol--after adjustment for sex, age, body mass index, alcohol consumption, oral contraceptive use, and serum albumin, triacylglycerol, and apolipoprotein A-I concentrations--additive genetic effects and shared common environment contributed 30.5% and 14.2% of the total variance, respectively. For serum alpha-tocopherol, approximately 22.1% of the total variance was due to the additive effects of genes and 18.7% to those of household environment, after adjustment for the covariates sex, age, vitamin E intake, oral contraceptive use, and cholesterol, triacylglycerol, and apolipoprotein A-I concentrations. For both vitamins, the influence of measured polymorphisms was not significant. Moreover, heritability and household effect estimates were not significantly different between the 4 classes of relatives and did not vary significantly when families shared more meals at home. Conclusions The results show that serum retinol and alpha-tocopherol concentrations are under genetic control in healthy families.

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD ( P =0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE e4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

Background In humans, a mutation of the leptin receptor gene (LEPR) leads to a rare obese syndrome of mendelian inheritance. However, obesity in humans results from interactions between genes and environment, mainly nutritional factors. Variations at the LEPR locus could be involved in the regulation of body weight. Design Genetic variations at the LEPR locus were screened in a selection of 30 French overweight subjects by Single Strand Conformation Polymorphism (SSCP) analysis, then an association study between genotypes and obesity phenotypes was performed in 179 French overweight patients recruited from the Nutrition Department of Bichat Hospital in Paris who were prescribed a low calorie diet and in 387 unrelated volunteers (98 overweight, 289 normal weight) drawn from the Stanislas Family Study in Nancy. Results Two new genetic variants were found: T + 70 C (exon 1) and Asp (A) 96 Asp (G) (exon 4). In Nancy, the T + 70 C polymorphism was associated with fat mass adjusted for BMI in women (P = 0·025). The genotype and allele frequencies of the Ser (T) 343 Ser (C) polymorphism (exon 9) were significantly different between normal and overweight women, with the T allele being more frequent in the overweight group (T frequency in Nancy, 0·82; in Nancy + Paris, 0·79) than in the normal weight group (0·69; P = 0·017 vs. Nancy overweight, P = 0·003 vs. Nancy + Paris overweight). In women from Nancy, fat mass adjusted for BMI was significantly associated with this polymorphism (P = 0·01). The overweight women carrying the C allele of this polymorphism lost more weight in response to low calorie diet than the non carriers (P = 0·006). Conclusions In women, genetic variations at the LEPR gene level are associated with overweight and fat mass in a cross sectional study and with response to low calorie diet in an intervention study. These results indicate that variations at the leptin receptor locus are associated with common obesity phenotypes and are a part of the polygenic influences on the response to nutritional environment.

Oral contraceptive (OC) use and common apo E polymorphism are well known to modify serum lipid and lipoprotein concentrations. The combined effect of OC use and apo E genotype on the concentration of apo E or apo C-III in apo B- (apo E-LpB or apo C-III-LpB) or in non-apo B-containing lipoparticles (apo E-Lp-non-B or apo C-III-Lp-non-B) are unknown. Our study comprised 613 women, aged 30-45 years, genotyped for common apo E polymorphism and who differed in their combined low-dose OC consumption. The concentrations of apo C-III, apo C-III-LpB and apo C-III-Lp-non-B were significantly higher in OC users than in non-users by 13, 23 and 8% respectively, without significant interaction with the apo E genotype. The concentrations of apo E and apo E-Lp-non-B were significantly lower (differences being -14% and -31% respectively) in OC users than in controls whereas the apo E-LpB concentration was significantly higher (+19%), resulting in a redistribution of apo E from Lp-non-B towards LpB. Total apo E and apo E-Lp-non-B concentrations were higher in subjects carrying the epsilon2 allele and lower in those with the epsilon4 allele when compared to epsilon3/epsilon3 subjects (P < 0.001). The opposite held for the apo E- LpB concentration (P < 0.05). The main finding is the significant interaction between apo E genotype and OC use (P < 0.01) on apo E-Lp-non-B concentration, the epsilon4 carriers showing the smallest differences between OC users and non-users in comparison with the epsilon2 or epsilon3/epsilon3 carriers. These results suggest that the common apo E polymorphism can modulate the OC use effect.

OBJECTIVE Association between blood pressure and triglyceride levels, and between lipoprotein lipase (LPL) (C/G)447 polymorphism and triglyceride levels has been described. We investigated whether the LPL (C/G)447 polymorphism was associated with blood pressure (BP) levels and longitudinal changes. DESIGN AND PARTICIPANTS For cross-sectional analysis, 767 men and 816 women (29-55 years) were selected from the Stanislas Cohort, a cohort of volunteers for a free health check-up. Only subjects without anti-hypertensive or lipid-lowering medication were included in the study. A subset of this sample population, 359 men and 337 women, had been followed during the 11 years prior to recruitment in the Stanislas Cohort and was used for longitudinal analysis. RESULTS The cross-sectional study showed that serum triglyceride levels differed significantly according to LPL genotypes in both genders, the G447 allele being associated with the lowest triglyceride levels (P < or = 0.01). Univariate and multivariate analysis found that LPL polymorphism was not related to BP levels in men. In contrast, women with the LPL-G447 allele had lower systolic (SBP) and pulse (PP) pressure levels than those with the LPL-CC genotype (P < or = 0.01 and P < or = 0.05, respectively); this association being independent of triglyceride level. The longitudinal study showed LPL genotype was an independent predictor of PP and SBP follow-up levels in women; changes over 11 years being lower for LPL-G447 allele carriers (P < or = 0.05). These associations were independent of triglyceride level. CONCLUSION The LPL-G447 allele was found associated with lower PP and SBP independently of triglyceride level in women. This result suggests that the LPL gene may influence blood pressure.

OBJECTIVES: To describe the eating patterns of members of French families and to assess the relationships between dietary intakes, eating style and overweight. DESIGN: Cross-sectional analysis of nutritional and behavioural characteristics. SUBJECTS: 1320 members of 387 families (age 11–65 y) attending the Centre for Preventive Medicine for a routine medical check-up. MEASUREMENTS: Individual body weight and height were measured. Food intake was assessed using a three day dietary record. Eating style was measured using the French validated version of the Dutch Eating Behaviour Questionnaire. RESULTS: In each of the four groups (men, women, boys and girls), dietary restraint was positively correlated with overweight (P≤0.001) and associated with lower energy intakes (P≤0.05–P≤0.001). A negative association between energy intake and overweight was found in girls only (P≤0.001). In all cases, overweight and dietary restraint exaggerated any existing macronutrient imbalance in energy intake (ie higher protein and fat contributions, lower carbohydrate contribution). Emotional eating was positively correlated to body mass index in women only (P≤0.01). External eating was mainly a characteristic of children (P≤0.001). CONCLUSION: As in overweight subjects, clear relationships were found in this sample of general population between dietary intakes and eating style. The population will be followed up for 10 y. In the long term, these results should have implications in the prevention of obesity.

Serum C-reactive protein (CRP) concentration was determined for 3605 subjects using an immunonephelometric assay improved to provide greater sensitivity. Subjects were from 5 to 75 years old and belonging to 1003 nuclear families recruited from the Stanislas Coh o rt Study between January 1994 and August 1995. Sample values for CRP ranged from 0.17 mg/l to 100 mg/l. Geometric means (mean − SD; mean + SD) were in the 5–14 years old group 0.37 (0.17–1.07) mg/l, in the 15–28 years old group 0.47 (0.17–1.38) mg/l and in the 29–75 years old group 0.98 (0.34–2.85) mg/l. For women, the geometric means were 0.38 (0.17–1.10) mg/l, 0.62 (0.20–1.90) mg/l and 0.98 mg/l (0.31–3.13) mg/l respectively. The interindividual variability ranged from 138% to 759% among different age classes. Biological factors associated with CRP concentration variations were examined and accounted for 25% of the CRP variability in men and 40% in women. The main biological factors statistically associated with CRP concentration variations in men were: drugs, leukocyte count, body mass index, tobacco consumption, age, and in women: drugs, leukocyte count, age, body mass index and hemoglobin concentration. These factors were used to define the exclusion and partition criteria when obtaining the reference samples. Medians for reference values ranged from 0.20 to 0.68 mg/l in males and from 0.20 to 0.78 mg/l in women.

As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the ε4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p

In order to assess the short- and long-term stability of apolipoprotein (apo) E concentration in serum, we compared the apo E concentrations measured in fresh human serum samples with those determined after storage at +4°C, −20°C or −80°C. The serum apo E concentration was measured by immunoturbidimetry using an anti-human apo E polyclonal antibody from goats. One week storage at +4°C did not significantly affect the serum apo E concentration. At −20°C or −80°C no significant change in apo E concentration occurred during up to three months of storage. Moreover, the concentration of apo E was not modified after long-term storage of serum samples kept at −196°C in liquid nitrogen for up to four years. In addition, 15 freeze-thaw cycles, over a 3-week period, did not affect the apo E concentration in serum. A similar freezethaw procedure applied to purified human recombinant apo E showed that apo E2 isoform was the most stable in comparison with the apo E3 and apo E4 isoforms.

To study carotid and femoral intima-media thicknesses and diameters in relation to age, sex, morphologic status and blood pressure.The subjects were 369 men and women (aged 10-54 years) from the Stanislas cohort, with no known cardiovascular disease.Intima-media thicknesses and diameters were measured by B-mode ultrasonography. The effects of sex, age, smoking, anthropometric variables, cholesterol and blood pressure were studied using bivariate and regression analysis.Carotid and femoral intima-media thicknesses were not affected by age nor by sex up to 18 years of age. Thereafter, they increased sharply in men and remained higher than in women. Values were correlated with systolic blood pressure only in men, and with fat-free mass in children and young adults only at the femoral site. Smoking, body mass index and fat mass were associated with intima-media thicknesses only in adults. Carotid diameter was little affected by age during childhood and in adults. Femoral diameter increased up to the age of 18 in both sexes and remained unaffected by age thereafter. This increase was more pronounced in boys, and so values became consistently greater in males aged over 14 years. Carotid diameter was correlated with body mass index or fat mass whereas femoral diameter was correlated with weight or fat-free-mass in children and men. The opposite was observed in women.Sex differences occur before adolescence for arterial diameter, but only at an adult age for intima-media thickness. In young subjects, carotid geometry seems to be influenced by blood pressure and excess body weight, while femoral artery geometry seems to be related to blood pressure and body growth.

Studies have shown contrasting results concerning the relation between carotid intima-media thickness (IMT) and apolipoprotein E (apo E) and angiotensin-converting enzyme (ACE) polymorphisms. Subjects, 76 men and 74 women, between 33 and 50 years, without any history of cardiovascular disease and without any anti-hypertensive or lipid lowering medication were selected from the Stanislas cohort. The IMT of carotid and femoral arteries were investigated by B-mode ultrasonography. The common apo E, (C/G) 447 lipoprotein lipase (LPL) and I/D ACE gene polymorphisms and serum ACE activity were determined. In the overall sample, male sex, age, systolic blood pressure, BMI, serum apo B level and tobacco consumption were positively correlated with carotid and femoral IMT. The common apo E polymorphism, the (C/G)LPL 447 polymorphism and ACE activity were not related to carotid and femoral IMT variability in either men or women. Unexpectedly, the I allele of the ACE gene was related to higher femoral IMT than the D allele in non-smokers only. Similar results were observed after adjustment for the main covariates of IMT variability. In conclusion, amongst our young adult sample the candidate risk factors for cardiovascular disease, apo e 4, C 447 -LPL and D-ACE alleles and ACE activity were not associated with increased carotid and femoral IMT.

The aim of this study was to assess the associ- ation between smoking, food consumption, and antioxidant vita- min intake and plasma indexes of oxidative stress and antioxi- dant defenses in French adults. Food and nutrient intakes of 459 healthy men aged 23-57 y were estimated by the diet history method and analyzed by smoking status. Plasma a-tocopherol, ascorbic acid, and carotenoids were measured as antioxidants and malondialdehyde, protein Schiff bases, and autoantibodies against malondialdehyde-protein adducts as oxidative stress indexes. Smokers ate less fruit and vegetables than nonsmokers, leading to lower vitamin E, vitamin C, and carotene intakes, even after adjustment for age, education, and marital status. Unlike vitamin E, plasma ascorbic acid and b-carotene concentrations were reduced in smokers compared with nonsmokers and were inversely related to cigarette consumption. This difference remained significant after adjustment for alcohol and dietary intakes. Among the measured oxidative stress indexes, only Schiff base concentration was positively related to the number of cigarettes smoked. In our sample of French men, smoking had an adverse effect on antioxidant status; vitamin intakes were reduced in smokers and plasma antioxidant indexes were altered independently of dietary intakes. As in other countries, in France smokers require particular attention in terms of public health intervention. Am J Clin Nutr 1998;67:231-9.

Drug consumption is sometimes used as a secondary judgment criterion for clinical trials. Many measurement methods are available to quantify drug consumption. Several methods were applied in a rheumatic disease trial involving 121 patients with chronic low back pain who lived around Saint-Nectaire, France, and who participated in the trial from April to November 1993 to determine an easily used and practical measurement method to detect a significant drug consumption change over time. Analgesic and nonsteroidal antiinflammatory drugs (NSAIDs) were classified according to the anatomical therapeutic chemical classification. Consumption was quantified on a weekly basis in number of tablets (method 1), unit of defined daily dose (method 2), milligrams of active principle (method 3), and NSAID equivalence score (method 4). These methods were applied in a randomized clinical trial of spa therapy on sufferers of chronic low back pain. An analysis of variance with repeated measures showed a significant difference in drug consumption between treatment and control groups detected by all methods, except for the NSAID consumption measured with method 3. The comparison of each method by the relative efficiency index indicated that method 1 had a greater sensitivity for detecting changes of drug consumption. Tablet count appears to be a more sensitive and more practical method for detecting a drug consumption change in clinical trials.

Segregation analysis using a regressive model with age- and sex-dependent effects was applied to family data of weight, fat mass (FM) and fat-free mass (FFM) to investigate the major gene hypothesis. The sample consisted of 220 nuclear families from the 'Stanislas Cohort' who volunteered for a free health examination (n = 913). FM and FFM were assessed by bioelectrical impedance. The data were adjusted for height2 and height prior to analysis. The spouse, father-offspring, mother-offspring and sib-sib correlations were: 0.16, 0.18, 0.25 and 0.32 for weight; 0.13, 0.20, 0.23 and 0.28 for FM; 0.18, 0.16, 0.29 and 0.41 for FFM. For the three phenotypes, models specifying a major gene with age- and sex-dependent effects and residual family correlations was better supported than models including only family correlations. For weight, the most parsimonious genetic model was a codominant model with a sex-dependent effect in parents and an age-increasing effect in offspring. For FM, the most parsimonious model was also a codominant model with sex-dependent effects in parents indicating higher effects in women than in men. For FFM, the most parsimonious model was a recessive model with no significant age or sex interaction, although the age interactions paralleled those observed on weight in offspring. For weight and FM, mendelian transmission was rejected. For FFM, the Mendelian and the environmental hypotheses were nearly equally supported and none was rejected when compared to general transmission. Then, evidence for a single major gene could not be inferred for any of the traits. This does not preclude the existence of several genes acting in a more complex way. However, our findings emphasize that weight is a composite phenotype reflecting different components which evolve in distinct ways during life span. For this reason, FM should be highly preferred to weight or BMI for the research of susceptibility genes to obesity.

Objective We assessed the associations of total dairy products; milk, yogurt, and cottage cheese; cheese; and calcium with 5-y changes in components of the metabolic syndrome. Methods Two hundred eighty-eight men and 300 women 28 to 60 y of age from the suivi temporaire annuel non invasif de la sante des lorrains assures sociaux (STANISLAS) cohort completed at baseline a 3-d dietary record. Statistics were performed using multivariate regression analysis. Results In men, no relation was found between the four dietary indices and components of the metabolic syndrome measured at baseline. Conversely, the consumption of milk, yogurt, and cottage cheese at entry was inversely associated with 5-y changes in glucose levels ( P ≤ 0.05, P ≤ 0.01 for sex interaction) and positively with 5-y changes in high-density lipoprotein cholesterol ( P ≤ 0.05). Higher calcium intakes were significantly related to a lower 5-y increase of the body mass index (BMI) and waist circumference in men ( P ≤ 0.01, P ≤ 0.05 for sex interaction). In addition, changes in diastolic blood pressure were inversely associated with the consumption of milk, yogurt, and cottage cheese only in men with a normal BMI ( P ≤ 0.05 for BMI interaction). In women, unlike men, associations were shown for some components measured at baseline: total dairy positively related to BMI and waist circumference; total dairy, milk, yogurt, and cottage cheese, and calcium were positively related to triacylglycerols and negatively to high-density lipoprotein cholesterol. However, no significant association was found for any 5-y-changes. Conclusion In men only, a higher consumption of dairy products was associated with positive changes in the metabolic profile in a 5-y period; a higher calcium consumption was associated with a lower 5-y increase of the BMI and waist circumference.

The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL3, CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37°C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e., HDL2b (9.71-12.90 nm), HDL2a (8.77-9.71 nm), HDL3a (8.17-8.77 nm), HDL3b (7.76-8.17 nm), and HDL3c (7.21-7.76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL2b (8.66 ± 2.34% versus 7.87 ± 1.83% in controls; p

The biological variation factors for cholesterol in circulating immune complexes (CIC-cholesterol) were studied in 941 unselected supposedly healthy volunteers, ages 4 to 78 years. We found a complex effect of age, including the existence of two peaks of CIC-cholesterol, one in males between 11 and 14 years and in females between 11 and 30 years, and in both sexes another peak between 41 and 60 years, and in both sexes a decrease between 31 and 40 years. By use of multiple regression analysis and after adjustment for age, CIC-cholesterol was positively related to plasma cholesterol concentration and leukocyte count, values being lower in females than in males and among subjects taking anti-inflammatory drugs. In addition, CIC-cholesterol was measured in 76 coronary angiography patients and in 100 supposedly healthy controls, ages 30 to 77 years. We noticed a significant increase (P < or = 0.05) of CIC-cholesterol when patients were affected by coronary stenosis between 20% and 50% (71.8 +/- 52.5 mumol/L vs 46.2 +/- 45.9 mumol/L in controls), but this was less pronounced in those with > 50% of obstruction (58.9 +/- 54.3 mumol/L); however, serum total cholesterol was not modified or even surprisingly slightly decreased in the coronary angiography individuals. Nevertheless, an important overlap of values in controls and patients makes questionable the usefulness of this variable in clinical practice.

Intercellular adhesion molecule-1 (ICAM-1) and E-, P-, and L-selectin are cellular adhesion molecules involved in the recruitment of leukocytes on the activated vessel wall during inflammation (1) and play an important role in the early stages of atherosclerosis and its complications (2). Thus, the measurement of soluble adhesion molecules in serum may have diagnostic relevance in many inflammatory diseases (3). A profile of soluble adhesion molecule concentrations may allow better therapeutic decisions in inflammatory and autoimmune disorders, infection, cancer, and cardiovascular pathologies and may also aid in the prediction of cardiovascular events (4)(5). However, the use of these markers in clinical practice depends critically on knowledge of their reference values. The purpose of the present study was to establish age- and sex-specific reference intervals for serum concentrations of soluble ICAM-1 and E-, P-, and L-selectin in healthy children (4–17 years) and adults (18–55 years). Blood samples were taken from healthy individuals (157 boys and 146 girls 4–17 years of age and 245 men and 250 women 18–55 years of age) who were members of the Stanislas cohort (6). Participants were of French origin (Vosges and Meurthe et Moselle); free from serious and/or chronic illnesses, especially cardiovascular, hepatic, or renal diseases; and were not on treatment with lipid-lowering drugs. Volunteers with aspartate aminotransferase, alanine aminotransferase, or γ-glutamyltransferase activities >200 U/L, apolipoprotein E concentrations >200 mg/L, orosomucoid or haptoglobin concentrations >3 g/L, cholesterol or triglyceride concentrations >10 mmol/L, C-reactive protein concentrations >30 mg/L, or glucose concentrations …

Background Polymorphisms of genes controlling cytokine production have not been studied in the genetic susceptibility to cutaneous adverse drug reactions (CADR). Objectives The objective was to determine whether polymorphisms in nine cytokine genes were associated to the occurrence of drug reaction with eosinophilia and systemic symptoms (DRESS) compared to drug-induced maculopapular eruption or urticaria and to controls without drug intolerance. Methods Results from 118 patients with a well-defined CADR were compared to 236 controls without drug intolerance living in the same area of France. We assessed nine polymorphisms: interleukin (IL)1-alpha-889C>T (rs 1800587), IL1-beta-511C>T (rs 16944), IL1-RN intron-2-VNTR (rs2234663), IL2-330T>G (rs 2069762), IL4-33C>T (rs 2070874), IL5-745C>T (rs 2069812), IL10-592C>A (rs 1800872), IL16-295T>C (rs 4778889) and tumour necrosis factor-alpha-308G>A (rs 1800629). Results Three polymorphisms exhibited a significant association with CADR (P

Background Very recently, we identified a novel polymorphism, rs2000999, located in haptoglobin gene (HP) as a strong genetic determinant of the haptoglobin levels (Hp). We aim to determine the reference values of Hp on the basis of its main sources of biological variation including the rs2000999 in a large French origin population, the STANISLAS Family Study (SFS). Methods Through a stepwise regression analysis, the main biological variables of Hp levels were identified in 3129 “apparently” disease-free individuals of the SFS. Hp reference ranges were subsequently established in a subgroup of 2923 selected healthy subjects, as the reference population. Results The plasma reference values of Hp ranged 0.08–1.97 g/L in males and 0.08–2.19 g/L in females. Gender, age, smoking, plasma levels of hemoglobin and the newly-discovered HP polymorphism, rs2000999, were found to be the strongest biological predictors of the Hp concentrations in human plasma. Hp levels, in both genders and in all age groups, were negatively associated with the presence and number of rs2000999 minor allele. Conclusion To be reliably interpretable in daily medical practice, the HP polymorphism, rs2000999, should be considered for partitioning its reference values. This polymorphism may also help for setting decision limits for medical interpretation of Hp concentrations.

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far.We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (P(overall) = 8.1 × 10(-59)), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23 ± 0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P(total cholesterol) = 0.002 and P(LDL) = 0.0008).Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact.

The question about differences in dietary patterns associated with beer, wine, and spirits is still unresolved. We used diet data from 423 middle-aged males of the STANISLAS Study. Using adjusted values for covariates, we observed a negative significant association between increasing alcohol intakes and the consumption of milk, yogurt, and fresh/uncured cheese, sugar and confectionery, vegetables and fruits, and a significant positive relationship with cheese, meat and organs, pork-butcher's meat, and potatoes. In addition, the first dietary pattern identified by factor analysis (characterized a more prudent diet) was inversely related to alcohol intakes. Conversely, when analyzing daily consumption of specific food groups and diet patterns according to beverage preference (wine, beer, and spirits), no significant difference was observed. In conclusion, in this sample of middle-aged French males, there was a linear trend between increasing alcohol intakes and worsening of quality of diet, while no difference was observed according to beverage preference.

Genome-wide linkage analysis studies reported the importance of the long arm of chromosome 13 in systolic blood pressure regulation. Therefore, isolating a genetic variant related to this chromosomal region could be challenging. Klotho KL-VS allele is located on this chromosomal region and its relationships with cardio-vascular risk factors need extensive investigations. The aim of the present study is to examine whether the klotho KL-VS genotype is associated with cardio-vascular risk factors, more particularly hypertension, in two independent cohorts. A secondary objective was to investigate relationships with antihypertensive treatment, arterial stiffness and carotid artery parameters.A total of 1023 French individuals were genotyped for klotho KL-VS. Participants were part of the French ERA and STANISLAS cohorts. In both cohorts, klotho KL-VS/KL-VS genotype was significantly associated with lower systolic blood pressure and pulse pressure when compared to homozygous and heterozygous more frequent (WT) allele carriers (p=0.003 and p0.001 respectively). Antihypertensive treatment stratification confirmed the previous significant associations, while a significant interaction between klotho KL-VS genotype and antihypertensive treatment was also interestingly found (0.019 for p interaction).Klotho KL-VS/KL-VS genotype may be associated with decreased cardio-vascular risk and may interact with antihypertensive treatment in order to reduce blood pressure. This finding could lead to identify subgroups of hypertensive adults who might benefit antihypertensive drug therapies.

BACKGROUND ABCB1 is a membrane transporter ubiquitously expressed particularly in peripheral blood mononuclear cells (PBMCs). Resistance to drugs is associated with genetic variations of its gene and with modulation of its expression through the pregnane-X-receptor (PXR) transcription factor. We have previously shown that ABCB1 polymorphisms were associated with blood lipid concentrations. METHODS We wanted to investigate the variation factors and the genetic determinants of ABCB1 and PXR expressions in PBMCs, and their interrelationships with plasma lipid levels. ABCB1 and PXR mRNA were quantified by real-time quantitative RT-PCR in PBMCs of 42 men and 39 women. RESULTS ABCB1 and PXR were both expressed in PBMCs of all individuals, but their expressions were not significantly correlated. ABCB1 mRNA was correlated with body mass index (BMI; p=0.01) and age (p=0.03). In women, lymphocyte count also correlated with ABCB1 transcripts (p

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 reassembling 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.

Background Human formyl peptide receptor 1 (FPR1) mediates inflammatory responses, recognized as important participants in the physiopathology of hypertension. Similarly, FPR1 C32T SNP is associated with inflammation and BP related pathways. Therefore, the relationship between FPR1 C32T SNP, BP and hypertension needs to be investigated. Method 1012 French middle-aged adults including 491 healthy individuals (5 years follow-up, T + 0 and T + 5 ) and 521 hypertensive individuals were PCR-RFLP genotyped for FPR1 C32T SNP (rs5030878). Results At entrance, there was no significant association between FPR1 C32T SNP and blood pressure (BP) in healthy individuals. However, 5 years later , significant associations were found for DBP, SBP (p 0.001 and p = 0.009 respectively) and for their 5 years changes (Δ) (p = 0.025 and p = 0.027 for DBP and SBP respectively). Significant interactions between FPR1 C32T SNP and age on DBP, SBP, ΔDBP and ΔSBP were found (p = 0.014, 0.008, 0.015 and 0.015 respectively). Consequently, stronger increase in BP was reported among healthy individuals aged less than 45 years. When normotensive individuals were compared to hypertensives ones, similar FPR1 C32T genotypes and allele frequency distributions were found. Conclusion FPR1 C32T SNP interacts with age, is associated with higher and a 5 years increase of BP levels in healthy individuals aged less than 45 years.

A segregation analysis using a regressive model with generation- and age-dependent effects was applied to familial data of height-adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check-up in the Preventive Medicine Center of Vandoeuvre-les-Nancy, France. The familial correlations were 0.094 +/- 0.040 between spouses, 0.198 +/- 0.023 between parent and offspring, and 0.327 +/- 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent-offspring and sib-sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene.

We studied the biological variability of blood superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPX; EC 1.11.1.9), and catalase (CAT; EC 1.11.1.6) in a sample of 1836 apparently health subjects, ages 4-97 years. SOD and GPX activities were assayed in plasma (P) and erythrocytes (E) by automated methods, and CAT was measured in erythrocytes by a manual technique. No statistically significant variation of these antioxidant enzyme activities according to gender was demonstrated, except for E-GPX, which was slightly but significantly higher in women than in men (P less than 0.001). Activities appear rather stable in adults less than 65 years old, but decrease for most enzymes in the elderly. There is no evidence that weight, blood pressure, or menopause influences the antioxidant enzymes' activities. In girls ages 10-14 years, E-SOD activity is reduced by 16% (P less than 0.05) after menarche. Variations related to smoking and alcohol consumption are slight and concern only P-SOD and P-GPX, respectively. Conversely, intake of some drugs (e.g., anti-inflammatory agents, antidepressants, and thyroid hormones) modifies activity of some of the three enzymes. E-SOD positively correlates with P-SOD (r = 0.216, P less than 0.001) and E-CAT (r = 0.123, P less than 0.001), and E-GPX with P-GPX (r = 0.218, P less than 0.001). Finally, we propose reference intervals for activities of the three antioxidant enzymes in blood in individuals less than 65 years old.

The purpose of this study was to investigate the familial resemblance for individual body circumferences (suprailiac, waist, thigh and arm) and for the waist/suprailiac (as surrogate for the waist/hip) and the waist/thigh circumference ratios, in a sample of 216 unselected nuclear families with children aged 10-25 years. Familial correlations were jointly computed, using the maximum-likelihood method. The highest familial resemblance was observed for the waist circumference and for the waist/suprailiac and the waist/thigh circumference ratios. There was no significant difference between father-offspring and mother-offspring correlations when considering individual body circumferences. In contrast, when considering the two ratios there was a stronger mother-child than father-child similarity. Furthermore, there was a higher resemblance of the mother with her daughter than with her son, but no significant sib sex difference in the father-offspring relationship. There was also a heterogeneity of sibling correlations for the two ratios, the like-sex pairs exhibiting higher correlations than the unlike-sex pairs. Lastly, the similarity observed between spouses, of similar magnitude to the father-offspring correlation, suggests the contribution of environmental rather than genetic factors for explaining the familial resemblance of the two ratios. In conclusion, the great family resemblance for the waist/suprailiac and the waist/thigh circumference ratios (correlations ranging from 0.23 to 0.68) appears remarkable, and should be taken in consideration, given the predictive value of these indices for disease in adulthood.