<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

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

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

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

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

Association of the rs6232 and rs6235 with obesity in children and adult populations.

<p>Data are n (%). All odds ratios and <i>P</i>-values were calculated by logistic regression analyses using non-obese individuals as reference group, adjusting for age, sex and DT2. <i>P</i>_add, <i>P</i>-values for the additive model.</p

Glucose homeostasis parameters in nondiabetic children and adult populations according to <i>PCSK1</i> rs6232.

<p>Data are means ± s.d. or medians (interquantile range). <i>P</i>-values were calculated by generalized linear regression. BMI was adjusted for age and gender. Plasma glucose/insulin levels and HOMA indices were adjusted for age, gender and BMI. HOMA-B, homeostasis model assessment of beta-cell function; HOMA-S, homeostasis model assessment of insulin sensitivity.</p

Glucose homeostasis parameters in nondiabetic children and adult populations according to <i>PCSK1</i> rs6235.

<p>Data are means ± s.d. or medians (interquantile range). <i>P_add</i>_-values were calculated by generalized linear regression using an additive model. BMI was adjusted for age and gender. Plasma glucose/insulin levels and HOMA indices were adjusted for age, gender and BMI. HOMA-B, homeostasis model assessment of beta-cell function; HOMA-S, homeostasis model assessment of insulin sensitivity.</p

Characteristics of the cases and controls in the children and adult populations.

<p>Data are means ± s.d. or medians (interquantile range). HOMA-B, homeostasis model assessment of beta-cell function; HOMA-S, homeostasis model assessment of insulin sensitivity.</p

Associations of 12 loci with BMI and WC in Mexican Adults and Children.

<p>Abbreviations: Chr, chromosome; RAF, risk allele frequency; SE, standard error; <i>P</i>-Het, <i>P</i>-heterogeneity; BMI, body mass index; WC, waist circumference. Effect values are presented as effect size per allele copy, except for <i>ADIPOQ, BCDIN3</i>/<i>FAIM2</i> and <i>BDNF</i> analyzed under a recessive model, where effect size is reported for two allele copies. <i>P</i>-values were adjusted for age and sex. Statistically significant associations are bold-faced.</p