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

Research output: Contribution to journalArticle

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

Fingerprint

Somatotropin Receptors
Hyperlipoproteinemia Type II
HDL Cholesterol
LDL Receptors
Laron Syndrome
Growth Hormone
Phenotype
Homozygote
Genes
Lipoproteins
Alleles
Mutation
Heterozygote
Insulin-Like Growth Factor I
LDL Cholesterol
Triglycerides
Cholesterol
Serum

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia : Intra-familial association study in an eight-generation hyperlipidemic kindred. / Takada, Daisuke; Ezura, Yoichi; Ono, Shuji; Iino, Yasuhiko; Katayama, Yasuo; Xin, Yuanpei; Wu, Lily L.; Larringa-Shum, Stacey; Stephenson, Susan H.; Hunt, Steven; Hopkins, Paul N.; Emi, Mitsuru.

In: American Journal of Medical Genetics, Vol. 121 A, No. 2, 30.08.2003, p. 136-140.

Research output: Contribution to journalArticle

Takada, D, Ezura, Y, Ono, S, Iino, Y, Katayama, Y, Xin, Y, Wu, LL, Larringa-Shum, S, Stephenson, SH, Hunt, S, Hopkins, PN & 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, vol. 121 A, no. 2, pp. 136-140.
Takada, Daisuke ; Ezura, Yoichi ; Ono, Shuji ; Iino, Yasuhiko ; Katayama, Yasuo ; Xin, Yuanpei ; Wu, Lily L. ; Larringa-Shum, Stacey ; Stephenson, Susan H. ; Hunt, Steven ; Hopkins, Paul N. ; Emi, Mitsuru. / Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia : Intra-familial association study in an eight-generation hyperlipidemic kindred. In: American Journal of Medical Genetics. 2003 ; Vol. 121 A, No. 2. pp. 136-140.
@article{37f72b69d48749ae8f11a5b1aba6fdd6,
title = "Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: Intra-familial association study in an eight-generation hyperlipidemic kindred",
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.",
keywords = "Familial hypercholesterolemia, Gene interaction, Growth hormone receptor, Modifier gene, SNP",
author = "Daisuke Takada and Yoichi Ezura and Shuji Ono and Yasuhiko Iino and Yasuo Katayama and Yuanpei Xin and Wu, {Lily L.} and Stacey Larringa-Shum and Stephenson, {Susan H.} and Steven Hunt and Hopkins, {Paul N.} and Mitsuru Emi",
year = "2003",
month = "8",
day = "30",
language = "English",
volume = "121 A",
pages = "136--140",
journal = "American Journal of Medical Genetics, Part A",
issn = "0148-7299",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia

T2 - Intra-familial association study in an eight-generation hyperlipidemic kindred

AU - Takada, Daisuke

AU - Ezura, Yoichi

AU - Ono, Shuji

AU - Iino, Yasuhiko

AU - Katayama, Yasuo

AU - Xin, Yuanpei

AU - Wu, Lily L.

AU - Larringa-Shum, Stacey

AU - Stephenson, Susan H.

AU - Hunt, Steven

AU - Hopkins, Paul N.

AU - Emi, Mitsuru

PY - 2003/8/30

Y1 - 2003/8/30

N2 - 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.

AB - 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.

KW - Familial hypercholesterolemia

KW - Gene interaction

KW - Growth hormone receptor

KW - Modifier gene

KW - SNP

UR - http://www.scopus.com/inward/record.url?scp=10744221701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744221701&partnerID=8YFLogxK

M3 - Article

C2 - 12910492

AN - SCOPUS:10744221701

VL - 121 A

SP - 136

EP - 140

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 0148-7299

IS - 2

ER -