Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Int J Cardiol. 2019 Mar 15;279:168-173. doi: 10.1016/j.ijcard.2018.09.107. Epub 2018 Oct 1.
Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population.
We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD.
Only two loci were associated with SUA levels: SLC2A9 (β = -0.47 mg/dl, P = 1.57 × 10 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group.
SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.
血清尿酸（SUA）是一种与心血管危险因素和冠状动脉疾病（CAD）相关的可遗传特征。全基因组关联研究（GWAS）已经确定了几个与 SUA 相关的基因，主要在欧洲人群中。然而，迄今为止，拉丁美洲人群的 GWAS 较少，SUA 相关单核苷酸多态性（SNP）在墨西哥人群中心血管疾病中的作用尚未得到研究。
我们在 2153 名墨西哥儿童和成人中进行了全基因组 SUA 关联研究，评估了遗传效应是否受到性别和肥胖的影响，并在一个独立的队列中使用孟德尔随机化方法研究了 SUA 修饰遗传变异在早发性 CAD 中的作用。
只有两个基因座与 SUA 水平相关：SLC2A9（β= -0.47mg/dl，P= 1.57×10-8，用于先导 SNP rs7678287）和 ABCG2（β= 0.23mg/dl，P= 2.42×10-8，用于先导 SNP rs2231142）。SLC2A9 rs7678287 和 ABCG2 rs2231142 基因型与肥胖之间没有明显的相互作用。然而，在成年人中观察到 ABCG2 rs2231142 基因型*性别相互作用显著（P= 0.001），但在儿童中没有观察到。尽管 SUA 水平与早发性 CAD、代谢综合征和肾小球滤过率（eGFR）降低相关，但只有 ABCG2 rs2231142 与早发性 CAD 组的 eGFR 降低相关。
SUA 升高与墨西哥人群中的早发性 CAD、代谢综合征和 eGFR 降低独立相关。然而，使用先导 SUA 相关 SNP（SLC2A9 和 ABCG2）的孟德尔随机化方法并不支持升高的 SUA 水平对早发性 CAD 的因果作用。
