Huertas-Vázquez A, del Rincón J P, Canizales-Quinteros S, Riba L, Vega-Hernández G, Ramírez-Jiménez S, Aurón-Gómez M, Gómez-Pérez F J, Aguilar-Salinas C A, Tusié-Luna M T
Unidad de Biología Molecular y Medicina Genómica del Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México y del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City.
Ann Hum Genet. 2004 Sep;68(Pt 5):419-27. doi: 10.1046/j.1529-8817.2003.00116.x.
Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families. We studied seven extended Mexican families with 153 members, including 64 affected subjects. A total of 11 markers were genotyped, including D1S104 which has been linked to FCHL in other studies. Two point linkage analysis for the FCHL phenotype, and for the elevated triglyceride (TG) trait, allowing for heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43) at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non-parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of 4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition, analysis of four candidate genes putatively involved in the expression of FCHL showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene cluster. However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families. In conclusion, our data confirm the involvement of a major susceptibility locus on chromosome 1q21-q23 in FCHL Mexican families, consistent with findings in other populations.
家族性混合性高脂血症（FCHL）是最常见的家族性血脂异常，在普通人群中的患病率为1%-2%。在芬兰、中国、德国和美国家族中，FCHL的一个主要基因座已被定位到1号染色体的1q21-q23区域。我们研究了7个大家庭，共153名成员，其中64名受影响个体。总共对11个标记进行了基因分型，包括在其他研究中已与FCHL连锁的D1S104。对FCHL表型和甘油三酯（TG）升高性状进行两点连锁分析，并考虑到基因异质性，在D1S2768（位于D1S104近端2.69 cM处）分别获得了最大HLOD值为1.67（α = 0.49）和1.93（α = 0.43）。对FCHL表型和TG性状进行基因异质性和非参数（NPL）多点分析，显示在D1S2768附近的最大HLOD值分别为1.27（α = 0.46）和1.64（α = 0.38），NPL值分别为4.00（P = 0.0001）和3.68（P = 0.0003）。此外，对4个可能参与FCHL表达的候选基因进行分析，未发现LCAT基因或APOA1/C3/A4/A5基因簇存在连锁证据。然而，我们不能排除这些基因以及LIPC和LPL基因作为次要易感基因座参与我们家族中FCHL、TG或总胆固醇（TC）升高性状表达的可能性。总之，我们的数据证实了1号染色体1q21-q23上的一个主要易感基因座参与了墨西哥FCHL家族的发病，这与其他人群的研究结果一致。
