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

Hiroshi Iijima, Mitsuru Emi, Manabu Wada, Makoto Daimon, Sayumi Toriyama, Satoru Koyano, Hidenori Sato, Paul N. Hopkins, Steven Hunt, Isao Kubota, Sumio Kawata, Takeo Kato

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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.

Original languageEnglish
Pages (from-to)193-200
Number of pages8
JournalJournal of Human Genetics
Issue number3
Publication statusPublished - Mar 2008
Externally publishedYes



  • Haplotype
  • Hepatic lipase
  • High-density lipoprotein cholesterol
  • Hyperalphalipoproteinemia
  • LIPC
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Iijima, H., Emi, M., Wada, M., Daimon, M., Toriyama, S., Koyano, S., Sato, H., Hopkins, P. N., Hunt, S., Kubota, I., Kawata, S., & Kato, T. (2008). Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations. Journal of Human Genetics, 53(3), 193-200.