Dietary fat and carbohydrate modulate the effect of the ATP-binding cassette A1 (ABCA1) R230C variant on metabolic risk parameters in premenopausal women from the Genetics of Atherosclerotic Disease (GEA) Study

Table S1. Demographic characteristics of the population. Table S2. Comparison of biochemical parameters stratified by gender and menopausal status. Table 3. Correlation between metabolic parameters and dietary macronutrients according to ABCA1/R230C genotypes in premenopausal women. Table S4. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes in the study population and premenopausal women. Table 5. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes and carbohydrate percentage tertiles in premenopausal women. Table 6. Comparison of biochemical parameters stratified by ABCA1/R230C genotypes and fat percentage tertiles in premenopausal women. (DOCX 162 kb

Comparison of biochemical parameters in individuals with premature coronary artery disease, subclinical atherosclerosis and controls.

<p>Data are expressed as means ± SD, log-transformed values were used for statistical analysis.</p>*<p><i>P</i> values were estimated using ANOVA for continuous variables and Pearson’s Chisquare test for categorical values.</p>†<p>Individuals with diagnosis of T2D were excluded from the analysis.</p><p>CAD: coronary artery disease; SA: subclinical atherosclerosis.</p

Association of the R230C/<i>ABCA1</i> variant with premature coronary artery disease and subclinical artherosclerosis.

<p>Associations were tested using logistic regression adjusting for age, gender, BMI and HDL-C levels.</p><p>SA: subclinical atherosclerosis; CAD: coronary artery disease; MAF: minor allele frequency.</p>†<p>Compared to controls.</p>‡<p>Compared to individuals with subclinical atherosclerosis.</p

Association of the R230C/<i>ABCA1</i> variant with quantitative metabolic parameters.

<p>Data are expressed as means ± standard deviation. Linear models were used adjusting for age, gender and BMI when appropriate based on log-transformed values.</p><p>TC: total cholesterol; TG: triglycerides; VAT/SAT ratio: visceral to subcutaneous adipose tissue ratio.</p

Associations of the R230C/<i>ABCA1</i> variant with metabolic risk factors for coronary artery disease.

<p>All associations were tested using logistic regression adjusting for age, gender and BMI when appropriate. (n) represents the number of cases with each trait.</p><p>MAF: minor allele frequency.</p

The Interaction of R230C and BMI Affects the Distribution of Abdominal Fat in Premenopausal Women.

<p>Lines represent simple linear regressions, blue lines represent RR genotypes and red lines represent C230 risk allele carriers (RC/CC genotypes). Premenopausal women with RR genotypes show a non-significant negative BMI-VAT/SAT correlation; however visceral fat correlated positively and significantly with BMI only in premenopausal women with RC and CC genotypes. BMI showed no correlation with abdominal fat distribution in menopausal women.</p

Demographic characteristics of the population.

<p>Data are expressed as means ± SD, log-transformed values were used for statistical analysis.</p>*<p><i>P</i> values were estimated using ANOVA for continuous variables and Pearson’s Chisquare test for categorical values.</p><p>CAD: coronary artery disease; SA: subclinical atherosclerosis.</p

Predicted VAT/SAT Ratio Values According to BMI in Premenopausal and Menopausal Women.

<p>Predicted visceral to subcutaneous adipose tissue ratio (VAT/SAT) values were calculated from regression models containing the <i>ABCA1</i>/R230C variant, BMI and the interaction term, adjusted for age. Blue lines represent RR genotypes and red lines represent C230 risk allele carriers (RC/CC genotypes). The interaction between the polymorphism and BMI was significant only in premenopausal women (<i>P</i> = 0.005).</p

The <em>ABCA1</em> Gene R230C Variant Is Associated with Decreased Risk of Premature Coronary Artery Disease: The Genetics of Atherosclerotic Disease (GEA) Study

<div><h3>Background</h3><p><em>ABCA1</em> genetic variation is known to play a role in HDL-C levels and various studies have also implicated <em>ABCA1</em> variation in cardiovascular risk. The functional <em>ABCA1</em>/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).</p> <h3>Aim</h3><p>The purpose of the study was to analyze whether the <em>ABCA1</em>/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.</p> <h3>Results</h3><p>The C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR = 0.566; <em>P_add</em> = 1.499×10⁻⁵). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (<em>P</em> = 0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (<em>P = </em>0.036).</p> <h3>Conclusion</h3><p>This is the first study assessing the effect of the R230C/<em>ABCA1</em> variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.</p> </div