Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families
Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families
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DOI：
10.1046/j.1529-8817.2003.00116.x
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发表时间：
2004-09-01
影响因子：
1.9
通讯作者：
Tusié-Luna, MT
中科院分区：
文献类型：
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作者：
Huertas-Vázquez, A;del Rincón, JP;Tusié-Luna, MT
家族性混合性高脂血症(FCHL)是最常见的家族性血脂异常，在一般人群中的患病率为1-2%。在芬兰、中国、德国和美国家庭中，FCHL的一个主要基因座已被定位在染色体1q21-q23上。我们研究了7个墨西哥大家庭的153名成员，其中包括的受试者。共有11个标记进行了基因分型，其中包括D1S104，该标记在其他研究中已与FCHL连锁。考虑到异质性，FCHL表型和甘油三酯(TG)升高性状的两点连锁分析显示，D1S2768(D1S104近端2.69 cM)的最大HLOD分别为1.67(α=0.49)和1.93(α=0.43)。FCHL表型和TG性状的异质性和非参数多点分析显示，在D1S2768附近，最大HLOD分别为1.2 7(α=0.46)和1.6 4(α=0.38)，NPL分别为4.0 0(P=0.0001)和3.68(P=0.0003)。此外，对四个可能参与FCHL表达的候选基因的分析表明，LCAT基因或APOA1/C3/A4/A5基因簇没有连锁的证据。然而，我们不能排除这些基因，或LIPC和LPL基因，作为FCHL表达的次要易感基因，或在我们的家族中参与甘油三酯或总胆固醇(TC)升高的性状。总之，我们的数据证实了染色体1q21-q23上的一个主要易感基因在FCHL墨西哥家庭中参与其中，这与在其他人群中的发现一致。
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.