Original Article | Published:

Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations

Journal of Human Genetics volume 53, pages 193200 (2008) | Download Citation


Hepatic lipase (HL) plays a major role in the regulation of plasma lipids. Several groups seeking to find association between the gene encoding HL (LIPC) and plasma concentrations of high-density lipoprotein cholesterol (HDLc) using various methods and populations have reported conflicting results. We have approached the problem of demonstrating a relationship between the LIPC locus and HDLc by means of haplotype association using four single nucleotide polymorphisms (SNPs) (rs12594375G/A, rs8023503C/T, rs4775047C/T, and rs11634134T/A) located in intron 1 of the LIPC gene in two independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively. Significant association between hyperalphalipoproteinemia and a specific haplotype in this intron was detected in both populations. When HDLc levels among the three haplotypic categories were analyzed [haplotype rs8023503C/rs12594375G (haplotype-1; H1) homozygotes (H1H1), haplotype rs8023503T/rs12594375A (haplotype-2; H2) homozygotes (H2H2), and heterozygotes (H1H2)], HDLc levels were lowest among H1H1 [mean ± standard error (SE) = 58.4 ± 0.4 mg/dl], highest among H2H2 (62.5 ± 0.8 mg/dl), and intermediate among H1H2 (59.2 ± 0.4 mg/dl) (P = 0.00011), indicating that H2 haplotype elevates plasma HDLc levels. This association was validated in the second population (n = 1,638) (P = 0.00070). The results provide convincing evidence that the LIPC locus influences HDL metabolism.

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  1. Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 992-9585, Japan

    • Hiroshi Iijima
    • , Mitsuru Emi
    • , Makoto Daimon
    • , Sayumi Toriyama
    • , Satoru Koyano
    •  & Hidenori Sato
  2. HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan

    • Hiroshi Iijima
    • , Mitsuru Emi
    • , Sayumi Toriyama
    • , Satoru Koyano
    •  & Hidenori Sato
  3. Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT, USA

    • Paul N Hopkins
    •  & Steven C Hunt
  4. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan

    • Isao Kubota
  5. Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan

    • Sumio Kawata


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Correspondence to Mitsuru Emi or Takeo Kato.

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