ABCA1 single nucleotide polymorphisms on high-density lipoprotein-cholesterol and overweight: the D.E.S.I.R. study.

The adenosine triphosphate-binding cassette A1 (ABCA1) gene plays a key role in reverse cholesterol transport. Some ABCA1 gene polymorphisms have been associated with high-density lipoprotein-cholesterol (HDL-C) concentrations. The aim of this study was to assess the effect of three polymorphisms, C69T, G378C, and G1051A (R219K), on HDL-C levels and their interaction with BMI in more than 5000 French whites from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort study. The T allele of the C69T single nucleotide polymorphism (SNP) was associated with higher HDL-C levels in normal-weight men (BMI <25 kg/m(2)). The C allele of the G378C SNP was associated with lower HDL-C in overweight subjects (BMI > or =25 kg/m(2)). For the G1051A SNP, in the normal-weight group, the minor A allele was significantly associated with higher HDL-C levels. In contrast, in overweight people, the minor allele was associated with lower HDL-C levels. After accounting for multiple testing, empiric p values remained significant for the associations between G378C SNP and HDL-C in the overweight group and between G1051A SNP and HDL-C in the normal-weight group. This study suggests that ABCA1 gene polymorphisms modulate HDL-C concentrations, in interaction with BMI, and, thus, they might influence cardiovascular risk in the general population.

Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study.

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.

Alcohol consumption and insulin resistance syndrome parameters: associations and evolutions in a longitudinal analysis of the French DESIR cohort.

PURPOSE: To determine the effects of average alcohol consumption and changes in alcohol intake on the insulin resistance syndrome parameters in a 3-year follow-up study. METHODS: Longitudinal study of 1856 and 1529 alcohol drinking men and women in the French DESIR study (Data from an Epidemiological Study on the Insulin Resistance syndrome), aged 30 to 64 years. RESULTS: In men, fasting glucose, body mass index, waist circumference, systolic blood pressure, and HDL-cholesterol were positively associated with average alcohol consumption while there was no association with insulin or triglycerides concentrations. A change in alcohol intake was positively associated with HDL-cholesterol concentration and systolic blood pressure at follow-up. These effects of alcohol could not be attributed specifically to the intake of wine. In women, while the alcohol HDL-cholesterol relation was similar to that found in the men, the only significant effect of average alcohol intake was an increase in systolic blood pressure, with a spurious decrease in blood pressure related to a 3-year increase in alcohol intake. CONCLUSIONS: Alcohol only provided a beneficial effect on HDL-cholesterol. The beneficial effect seen by other authors of moderate alcohol drinking on diabetes and cardiovascular risk may be due to effects on parameters other than those included in the current definitions of the insulin resistance syndrome.