Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: Intra-familial association study in an eight-generation hyperlipidemic kindred

Daisuke Takada, Yoichi Ezura, Shuji Ono, Yasuhiko Iino, Yasuo Katayama, Yuanpei Xin, Lily L. Wu, Stacey Larringa-Shum, Susan H. Stephenson, Steven Hunt, Paul N. Hopkins, Mitsuru Emi

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16 Citations (Scopus)

Abstract

Defect of growth hormone receptor (GHR) is classically known to cause Laron syndrome, characterized by short stature, specific facial appearance, elevated serum growth hormone levels, and decreased insulin-like growth factor I levels. In addition, an increased cardiovascular risk due to elevated plasma total and LDL cholesterol levels marks another feature of the disease. Growth hormone (GH) plays an important role in the regulation of lipoprotein metabolism. GH status was found to be an independent determinant of plasma total cholesterol and triglyceride levels in humans. We studied a total of 207 members of eight-generation extended family of familial hypercholesterolemia (FH) in which affected members presented with various lipoprotein phenotypes. Intra-familial correlation analysis of a modifier effect of a Leu526Ile substitution in GHR gene was carried out among 95 carriers for LDL receptor gene (LDLR) mutation and 112 non-carriers. When plasma high-density lipoprotein cholesterol (HDL-c) levels in the LDLR-mutation carriers were compared, a significant lowering effect of HDL-c was observed with the Leu allele; the values were lowest among Leu/Leu homozygotes (mean ± SD = 37 ± 2 mg/dl), highest in Ile/Ile homozygotes (50 ± 4 mg/dl), and intermediate among Leu/Ile heterozygotes (41 ± 2 mg/dl) (P = 0.0021). The results indicate a significant modification of the phenotype of FH with the defective LDLR allele, by GHR Leu variation in the kindred studied.

Original languageEnglish
Pages (from-to)136-140
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume121 A
Issue number2
Publication statusPublished - 30 Aug 2003
Externally publishedYes

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Keywords

  • Familial hypercholesterolemia
  • Gene interaction
  • Growth hormone receptor
  • Modifier gene
  • SNP

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Takada, D., Ezura, Y., Ono, S., Iino, Y., Katayama, Y., Xin, Y., Wu, L. L., Larringa-Shum, S., Stephenson, S. H., Hunt, S., Hopkins, P. N., & Emi, M. (2003). Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: Intra-familial association study in an eight-generation hyperlipidemic kindred. American Journal of Medical Genetics, 121 A(2), 136-140.