Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus

The NHLBI family heart study

Hilary Coon, Richard H. Myers, Ingrid B. Borecki, Donna K. Arnett, Steven Hunt, Michael A. Province, Luc Djousse, Mark F. Leppert

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing, among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.

Original languageEnglish
Pages (from-to)2275-2280
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number10
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Familial Combined Hyperlipidemia
National Heart, Lung, and Blood Institute (U.S.)
Apolipoprotein A-I
Chromosomes
Lod Score
Alleles
Lipoprotein Lipase
Chromosomes, Human, Pair 1
Dyslipidemias
Genetic Markers
LDL Cholesterol
Genes
Coronary Disease
Mutation

Keywords

  • Coronary disease
  • Genetic linkage
  • Hyperlipidemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus : The NHLBI family heart study. / Coon, Hilary; Myers, Richard H.; Borecki, Ingrid B.; Arnett, Donna K.; Hunt, Steven; Province, Michael A.; Djousse, Luc; Leppert, Mark F.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 20, No. 10, 2000, p. 2275-2280.

Research output: Contribution to journalArticle

Coon, Hilary ; Myers, Richard H. ; Borecki, Ingrid B. ; Arnett, Donna K. ; Hunt, Steven ; Province, Michael A. ; Djousse, Luc ; Leppert, Mark F. / Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus : The NHLBI family heart study. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 ; Vol. 20, No. 10. pp. 2275-2280.
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abstract = "Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20{\%} of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing, among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.",
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T1 - Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus

T2 - The NHLBI family heart study

AU - Coon, Hilary

AU - Myers, Richard H.

AU - Borecki, Ingrid B.

AU - Arnett, Donna K.

AU - Hunt, Steven

AU - Province, Michael A.

AU - Djousse, Luc

AU - Leppert, Mark F.

PY - 2000

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N2 - Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing, among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.

AB - Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing, among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.

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