Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study.

The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (<255Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex (p=0.008, p=0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex (p=0.005, p=0.004 and p=0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study.

BACKGROUND: Adiponectin expression and plasma concentrations are decreased in human and animal models of obesity. Several single nucleotide polymorphisms (SNPs) in the adiponectin gene are known to influence the plasmatic concentration of the encoded protein. Some of these adiponectin polymorphisms have been associated with BMI in cross-sectional studies. OBJECTIVE: The aim of our study was to examine the longitudinal relationships between adiponectin gene polymorphisms and anthropometric indices. DESIGN: Two adiponectin gene (ADIPOQ) SNPs, -11391G>A and -11377C>G, were genotyped in 837 French Caucasian subjects from the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort. Anthropometric scores were measured at three clinical examinations over a 7-year period. RESULTS: For -11391G>A as well as for -11377C>G, we detected no association between the variant allele and anthropometric measurements at baseline. Considering longitudinal effects, we detected moderately higher waist-to-hip ratio (WHR) changes for the carriers of the -11391A (P=0.02) and -11377C (P=0.03) allele over the follow-up of the study. -11391G>A and -11377C>G define haplotypes associated also with WHR measurements and their changes over the follow-up of the study. Diploid configurations that combine -11391A and -11377C were associated with significantly higher WHR changes (DeltaCE: P=0.02) compared to other haplotypes. In addition, higher adiponectin levels were observed in AC/AC diplotypes compared to GG/GG carriers (P<0.0001). CONCLUSION: In the SU.VI.MAX study, genetic variations in the adiponectin gene affect abdominal fat gain over life span.

Detection of interproximal caries using methods applicable to a field environment: digital radiography, manually processed film, and self-developing film.

The purpose of this study was to determine if the alternatives to conventional dental radiography are diagnostically equivalent to conventional film in a field setting. These alternatives, digital radiography and self-developing film, could significantly decrease the weight and cubic size of a field X-ray set. Five radiographic methods were evaluated: self-developing film, manually processed film, film developed in an automatic processor, digital images on a liquid crystal diode, and digital images on a cathode ray tube screen. The results indicate that the liquid crystal diode system adversely affected the ability of the dentist to detect small interproximal lesions. The other methods were statistically equivalent. A recommendation for an "image acquisition" system to be included in a field dental treatment facility should be based on clinical factors as well as nonclinical factors such as cost, reliability, and logistical support requirements.

Interactions between dietary fat intake and FASN genetic variation influence LDL peak particle diameter.

BACKGROUND: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on the Quebec Family Study (QFS) revealed a quantitative trait locus for LDL peak particle diameter (LDL-PPD) on the 17q21 region. A positional candidate gene - the fatty acid synthase gene (FASN) - encodes a key enzyme in the biogenesis of membrane lipids. FASN may play a role in the regulation of feeding and may be a potential therapeutic target for obesity and insulin resistance. METHODS: Analyses were performed on 592 subjects of the QFS. Dietary fat was estimated by a 3-day food record. LDL-PPD was measured by gradient gel electrophoresis on polyacrylamide gradient gels. RESULTS: Five single nucleotide polymorphisms were genotyped in FASN gene. FASN rs4246444 was associated with LDL-PPD, but only when fat intake was taken into account (p = 0.001). High and low lipid consumers were defined using a cutoff of 35% of dietary fat intake. Carriers of the variant allele showed smaller LDL-PPD only when consuming a high amount of fat. This association remained significant after adjustments for age, sex, body mass index and plasma triglyceride levels. CONCLUSION: The results suggest that dietary fat intake may modify the effect of the FASN rs4246444 polymorphism on LDL-PPD.

Influences of the phosphatidylcholine transfer protein gene variants on the LDL peak particle size.

BACKGROUND: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) affecting LDL peak particle size (LDL-PPD) and density on the 17q21 region. This region contains the phosphatidylcholine transfer protein gene (PCTP). In the liver, phosphatidylcholine transfer protein binds specifically phosphatidylcholine suggesting a role for this protein in the formation of HDL and possibly VLDL phospholipid membranes. OBJECTIVES: To test the association between two coding polymorphisms (c.29A>C (Glu10Ala) and c.188G>A (Cys63Tyr)) in PCTP gene and the LDL-PPD. METHODS: LDL-PPD was measured by non-denaturating 2-16% polyacrylamide gradient gel electrophoresis on 623 QFS subjects. RESULTS: After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD than A/A homozygotes (p<0.05). These results remained significant when LDL-PPD was further adjusted for the effects of BMI and triglyceride levels (p<0.04). We also observed a three-fold lower risk of having the small (LDL-PPD <256A), dense LDL phenotype in subjects carrying the c.29C allele, when compared to A/A homozygotes (OR=0.35 (95% CI: 0.14-0.91; p=0.03)). CONCLUSION: PCTP gene variants are associated with LDL-PPD.