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

BackgroundVNN1 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 VNN1 gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children. Methodology/Principal FindingsVNN1 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 VNN1 mRNA expression levels (P = 2.9 × 10−5), decreased HDL-C levels (β = −6.19, P = 0.028) and with higher body mass index (BMI) z-score (β = 0.48, P = 0.024) in the total sample. In addition, VNN1 expression showed a positive correlation with HDL-C levels (r = 0.220; P = 0.017) and a negative correlation with BMI z-score (r = −0.225; P = 0.015) only in girls. Conclusion/SignificanceOur data suggest that VNN1 gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls.背景：VNN1基因表达水平及G-137T多态性与墨西哥裔美国成年人的高密度脂蛋白胆固醇（High Density Lipoprotein Cholesterol, HDL-C）水平相关。本研究旨在评估VNN1基因表达与G-137T变异对墨西哥青春期前儿童HDL-C及其他代谢性状的影响。 方法与主要结果：对224名年龄6~8岁的无亲缘关系墨西哥梅斯蒂索儿童（男107名，女117名）的外周血白细胞进行VNN1信使核糖核酸（messenger RNA, mRNA）表达水平定量，并对G-137T变异（rs4897612）进行基因分型。为校正群体分层，分析了包含10个祖先信息标记的检测面板。对族群混杂进行校正后，在全部研究样本中，TT基因型与较低的VNN1 mRNA表达水平（P=2.9×10⁻⁵）、降低的HDL-C水平（β=-6.19，P=0.028）以及更高的体重指数（Body Mass Index, BMI）z评分（β=0.48，P=0.024）显著相关。此外，仅在女童亚组中，VNN1表达与HDL-C水平呈正相关（r=0.220；P=0.017），与BMI z评分呈负相关（r=-0.225；P=0.015）。 结论与意义：本研究数据表明，VNN1基因表达及G-137T变异与墨西哥儿童的HDL-C水平相关，尤其在青春期前女童中更为显著。