Expression of Apolipoprotein(a) Gene is Regulated by 5'-Haplotype rather than TTTTA Repeat

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  • アポリポプロテイン(a)遺伝子発現はTTTTA反復配列よりも5'-ハプロタイプによって制御される
  • アポリポプロテイン(a) イデンシ ハツゲン ワ TTTTA ハンプク ハイレツ ヨリモ 5'-ハプロタイプ ニ ヨッテ セイギョ サレル

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論文(Article)

A high plasma level of lipoprotein(a), Lp(a), is recognized as an independent risk factor for various atherothrombotic diseases. Lp(a) concentrations are under genetic control, especially by the sizes of apolipoprotein(a), apo(a). However, marked differences in plasma Lp(a) levels are present among subjects having the same apo(a) sizes. It has been reported that Lp(a) concentrations are also affected by four haplotypes (types A-D) of the apo(a) gene in its 5'-flanking region (5-FL), and a (TTTTA)n repeat (pentanucleotide repeat, PNR) upstream of these SNPs (Single nucleotide polymorphisms). Thus, we explored the relationship between 5-FL haplotypes and PNRs among Japanese individuals. Strong linkage disequilibrium was observed between the haplotypes and PNRs. 8 PNRs and 9 PNRs were associated with types A and C (8-A and 8-C) and type D (9-D), respectively. 8-C had higher Lp(a) levels than 9-D among healthy individuals and patients with ischemic heart disease. Luciferase reporter assays revealed that the difference in transcriptional efficiency of apo(a) gene between 8-C and 8-D was more distinct than that between 8-D and 9-D. Gel sift assays also suggested that 8-C had higher binding affinity to transcription factors than 9-D. Accordingly, the 5-FL haplotype rather than the PNR plays an important role in regulating plasma Lp(a) concentrations.

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