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辨识出第一个高脂血症基因

家族性混合型高脂血症(FCHL)是易致冠心病常见的原因之一。其特征是胆固醇和甘油三酯增高。

美国加洲大学的Paivi Pagukanta--以前的研究曾发现染色体1的一个区域有一个或多个基因与FCHL危险增高有关。他们分析了芬兰的60个有该种情况的家族,确认出此疾病常有一个编码"上游转录因子1"(USF1)基因,与高甘油三酯男子的关联最强。

USF1蛋白调节几个基因,包括几个参与葡萄糖和脂质代谢的基因。似与FCHL有关。USF1与脂质有3种关联:增加apoB、增加总胆固醇水平和小LDL脂蛋白的颗粒大、小峰值。据此,作者称"这些结果意味着USF1参与FCHL的复杂脂质异常的特征"。

鉴于同一个染色体区域亦与2型糖尿病有关,这就提出了USF1基因亦参与代谢综合征和糖尿病的可能性。

结论:"FCHL和2型糖尿病的临床特征的核心是葡萄糖耐量不正常、高脂血症、胰岛素抗性和高血压。USF1很可能与此有关"

Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1).

Pajukanta P, Lilja HE, Sinsheimer JS, Cantor RM, Lusis AJ, Gentile M, Duan XJ, Soro-Paavonen A, Naukkarinen J, Saarela J, Laakso M, Ehnholm C, Taskinen MR, Peltonen L.

Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095-7088, USA.

Familial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both, is observed in about 20% of individuals with premature coronary heart disease. We previously identified a locus linked to FCHL on 1q21-q23 in Finnish families with the disease. This region has also been linked to FCHL in families from other populations as well as to type 2 diabetes mellitus. These clinical entities have several overlapping phenotypic features, raising the possibility that the same gene may underlie the obtained linkage results. Here, we show that the human gene encoding thioredoxin interacting protein (TXNIP) on 1q, which underlies combined hyperlipidemia in mice, is not associated with FCHL. We show that FCHL is linked and associated with the gene encoding upstream transcription factor 1 (USF1) in 60 extended families with FCHL, including 721 genotyped individuals (P = 0.00002), especially in males with high triglycerides (P = 0.0000009). Expression profiles in fat biopsy samples from individuals with FCHL seemed to differ depending on their carrier status for the associated USF1 haplotype. USF1 encodes a transcription factor known to regulate several genes of glucose and lipid metabolism.

Nat Genet. 2004 Apr;36(4):371-6. [标签:content1][标签:content2]

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作者:admin@医学,生命科学    2011-06-02 17:14
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