Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy–Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.

中文翻译：

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SLC22A1 的遗传变异与墨西哥女性的血脂水平有关

血脂异常是冠状动脉疾病的主要危险因素，其特征是脂质浓度的改变，包括低密度脂蛋白胆固醇 (LDL-c)、高密度脂蛋白胆固醇 (HDL-c) 和三酰基甘油。已经证明了几个基因参与血脂异常的发展。SLC22A1的遗传变异与胆固醇和 LDL-c 水平升高有关。本研究的目的是评估SLC22A1基因中的单核苷酸多态性 (SNP) 与墨西哥女性致动脉粥样硬化风险脂质水平之间的关联。进行了人体测量和生化测量，以及SLC22A1中的四个 SNP通过实时聚合酶链反应进行基因分型。验证了 Hardy-Weinberg 平衡，并计算了单倍型频率。我们发现分析的 SNP 的等位基因频率与墨西哥和世界上报告的 SNP 的等位基因频率存在显着差异，这可能是由于所研究女性的历史混合存在差异。评估广义线性模型以确定基因型和单倍型与脂质水平之间的关联。我们发现，在携带多态性 rs628031 和 rs594709 的 GA 和 AG 基因型的女性中，总胆固醇和 LDL-c 水平显着增加，显性遗传模型中也显示了显着影响。有趣的是，我们确定了 AGC-GAT 单倍型与 LDL-c 水平升高和 AGA-GAT 单倍型与 HDL-c 水平升高之间的重要关系。另一方面，我们发现所研究的多态性之间存在很强的连锁不平衡。我们的结果表明，在SLC22A1基因影响致动脉粥样硬化风险脂质的血清水平，表明这些变异可能影响有机阳离子转运蛋白 1 的功能，从而影响脂质代谢的调节。