<em>VNN1</em> Gene Expression Levels and the G-137T Polymorphism Are Associated with HDL-C Levels in Mexican Prepubertal Children

<div><h3>Background</h3><p><em>VNN1</em> gene expression levels and the G-137T polymorphism have been associated with high density lipoprotein cholesterol (HDL-C) levels in Mexican American adults. We aim to evaluate the contribution of <em>VNN1</em> gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children.</p> <h3>Methodology/Principal Findings</h3><p><em>VNN1</em> mRNA expression levels were quantified in peripheral blood leukocytes from 224 unrelated Mexican-Mestizo children aged 6–8 years (107 boys and 117 girls) and were genotyped for the G-137T variant (rs4897612). To account for population stratification, a panel of 10 ancestry informative markers was analyzed. After adjustment for admixture, the TT genotype was significantly associated with lower <em>VNN1</em> mRNA expression levels (<em>P</em> = 2.9 × 10⁻⁵), decreased HDL-C levels (β = −6.19, <em>P</em> = 0.028) and with higher body mass index (BMI) z-score (β = 0.48, <em>P</em> = 0.024) in the total sample. In addition, <em>VNN1</em> expression showed a positive correlation with HDL-C levels (r = 0.220; <em>P</em> = 0.017) and a negative correlation with BMI z-score (r = −0.225; <em>P</em> = 0.015) only in girls.</p> <h3>Conclusion/Significance</h3><p>Our data suggest that <em>VNN1</em> gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls.</p> </div

Association of G-137T variant with metabolic parameters stratified by gender.

<p>Effect values are presented as effect for two T copies (recessive model), standard error (SE). Genotype frequencies: all children (GG, 41.1%; GT, 47.7%; TT, 11.2%); boys (GG, 42.1%; GT, 49.5%; TT, 8.4%); girls (GG, 40.2%; GT, 46.1%; TT, 13.7%). BMI, body mass index; FM, percent fat mass; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol.</p>a<p><i>P</i>-values adjusted for admixture in all tests and for BMI z-score when appropriate.</p>*<p>Significant after Bonferroni correction.</p

Correlation of <i>VNN1</i> mRNA levels in leukocytes with metabolic phenotypes.

<p>BMI, body mass index; FM, percent fat mass; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol.</p>a<p><i>P</i>-values adjusted for admixture.</p>*<p>Significant after Bonferroni correction.</p

Effect of G-137T variant on <i>VNN1</i> expression levels in Mexican prepubertal children.

<p>The results are presented as the global mean ± the standard error.</p

Anthropometric and biochemical parameters according to gender.

<p>Data are means ± s.d. or n (%). BMI, body mass index; FM, percent fat mass; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; HA, hypoalphalipoproteinemia.</p>a<p><i>P</i>-values were calculated by t-test;</p>b<p>X² test.</p

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

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

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

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