Huertas-Vazquez Adriana, Aguilar-Salinas Carlos, Lusis Aldons J, Cantor Rita M, Canizales-Quinteros Samuel, Lee Jenny C, Mariana-Nuñez Lizzette, Riba-Ramirez Roopa-Metha Laura, Jokiaho Anne, Tusie-Luna Teresa, Pajukanta Päivi
Molecular y Medicina Genómica del Instituto de Investigaciones Biomédicas, UNAM, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico.
Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1985-91. doi: 10.1161/01.ATV.0000175297.37214.a0. Epub 2005 Jun 23.
To investigate the largely unknown genetic component of the common lipid disorder, familial combined hyperlipidemia (FCHL) in Mexicans, we analyzed the upstream transcription factor 1 (USF1) gene that was recently associated with FCHL and high triglycerides (TG) in Finns. We also analyzed the Mexican FCHL families for 26 microsatellite markers residing in the seven chromosomal regions on 2p25.1, 9p23, 10q11.23, 11q13, 16q24.1, 19q13, and 21q21, previously linked to FCHL in whites.
We genotyped 314 individuals in 24 Mexican families for 13 SNPs spanning an 88-kb region, including USF1. The FCHL and TG traits showed significant evidence for association with 3 SNPs, hCV1459766, rs3737787, and rs2073658, and haplotype analyses further supported these findings (probability values of 0.05 to 0.0009 for SNPs and their haplotypes). Of these SNPs, hCV1459766 is located in the F11 receptor (F11R) gene, located next to USF1, making it difficult to exclude. Importantly, the association was restricted to a considerably smaller region than in the Finns (14 kb versus 46 kb), possibly because of a different underlying linkage disequilibrium structure. In addition, 1 of the 7 regions, 16q24.1, showed suggestive evidence for linkage (a lod score of 2.6) for total cholesterol in Mexicans.
This study, the first to extensively investigate the genetic component of the common FCHL disorder in Mexicans, provides independent evidence for the role of USF1 in FCHL in an outbred population and links the 16q24.1 region to an FCHL-component trait in Mexicans.
为研究常见脂质紊乱疾病——墨西哥人群中的家族性混合性高脂血症（FCHL）中很大程度上未知的遗传成分，我们分析了上游转录因子1（USF1）基因，该基因最近被发现与芬兰人群中的FCHL及高甘油三酯（TG）有关。我们还对墨西哥FCHL家族中位于2p25.1、9p23、10q11.23、11q13、16q24.1、19q13和21q21这7个染色体区域的26个微卫星标记进行了分析，这些区域先前在白种人中与FCHL相关联。
我们对24个墨西哥家族中的314名个体进行基因分型，检测包括USF1在内的跨越88 kb区域的13个单核苷酸多态性（SNP）。FCHL和TG性状显示出与3个SNP，即hCV1459766、rs3737787和rs2073658显著相关，单倍型分析进一步支持了这些发现（SNP及其单倍型的概率值为0.05至0.0009）。在这些SNP中，hCV1459766位于紧邻USF1的F11受体（F11R）基因中，难以排除其关联。重要的是，与芬兰人群相比，关联区域明显更小（14 kb对46 kb），这可能是由于潜在的连锁不平衡结构不同所致。此外，7个区域中的1个，即16q24.1，显示出在墨西哥人群中总胆固醇存在连锁的提示性证据（对数优势分数为2.6）。
本研究首次广泛调查了墨西哥人群中常见FCHL疾病的遗传成分，为USF1在非近亲繁殖人群的FCHL中的作用提供了独立证据，并将16q24.1区域与墨西哥人群中的一种FCHL成分性状联系起来。
