Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population

Nicola Longo, Yuhuan Wang, Shelley A. Smith, Sharon D. Langley, Linda DiMeglio, Daniel Giannella-Neto

Research output: Contribution to journalArticle

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Abstract

We studied the association between common haplotypes in six relevant lipid metabolism genes with plasma lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic triglyceride lipase (HL), low-density lipoprotein cholesterol receptor (LDLR), apolipoprotein E (ApoE) and lecithin-cholesterol acyltransferase (LCAT) genes, and studied 732 individuals from 184 German families. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) were similar to those reported in other European and American populations. Haplotypes derived from SNP combinations resulted in more significance and of a higher degree than did single SNPs in the genotype-phenotype association analysis. Reduction of the polygenic variance attributable to haplotypes was estimated using variance components analysis. Under the biometrical genetic model, allelic association of haplotypes was highly significant for HDL, LDL and the LDL/HDL ratio. The residual kinship correlation was reduced accordingly. The ApoE gene had a strong effect on trait variation; however, the other genes also contributed substantially. An epistatic interaction could not be demonstrated in this sample. The data are consistent with the notion that common genetic variants influence common traits.

Original languageEnglish
JournalHuman Molecular Genetics
Volume11
Issue number12
StatePublished - Jun 1 2002

Fingerprint

LDL Cholesterol
Haplotypes
HDL Cholesterol
Cholesterol
Single Nucleotide Polymorphism
Apolipoproteins E
Population
Genes
Cholesterol Ester Transfer Proteins
Phosphatidylcholine-Sterol O-Acyltransferase
Lipoprotein Lipase
LDL Receptors
Genetic Models
Genetic Association Studies
Lipase
Lipid Metabolism
Analysis of Variance
Lipids
Liver

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population. / Longo, Nicola; Wang, Yuhuan; Smith, Shelley A.; Langley, Sharon D.; DiMeglio, Linda; Giannella-Neto, Daniel.

In: Human Molecular Genetics, Vol. 11, No. 12, 01.06.2002.

Research output: Contribution to journalArticle

Longo, Nicola ; Wang, Yuhuan ; Smith, Shelley A. ; Langley, Sharon D. ; DiMeglio, Linda ; Giannella-Neto, Daniel. / Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 12.
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