Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p

Hooman Allayee, Tjerk W A De Bruin, K. Michelle Dominguez, Li S C Cheng, Eli Ipp, Rita M. Cantor, Kelly L. Krass, Eric T P Keulen, Bradley E. Aouizerat, Aldons J. Lusis, Jerome I. Rotter

Research output: Contribution to journalArticle

Abstract

Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, α-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic α-adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.

Original languageEnglish (US)
Pages (from-to)773-778
Number of pages6
JournalHypertension
Volume38
Issue number4
StatePublished - 2001

Fingerprint

Chromosomes
Genome
Blood Pressure
Lod Score
Chromosomes, Human, Pair 4
Dyslipidemias
Nonesterified Fatty Acids
Genes
Familial Combined Hyperlipidemia
Insulin
Hypertension
Lipids
Lipoprotein Lipase
Apolipoproteins B
Population
Insulin Resistance
Animal Models

Keywords

  • Dyslipidemia
  • Genetics
  • Genome scan
  • Hypertension, essential
  • Linkage analysis

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Allayee, H., De Bruin, T. W. A., Dominguez, K. M., Cheng, L. S. C., Ipp, E., Cantor, R. M., ... Rotter, J. I. (2001). Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. Hypertension, 38(4), 773-778.

Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. / Allayee, Hooman; De Bruin, Tjerk W A; Dominguez, K. Michelle; Cheng, Li S C; Ipp, Eli; Cantor, Rita M.; Krass, Kelly L.; Keulen, Eric T P; Aouizerat, Bradley E.; Lusis, Aldons J.; Rotter, Jerome I.

In: Hypertension, Vol. 38, No. 4, 2001, p. 773-778.

Research output: Contribution to journalArticle

Allayee, H, De Bruin, TWA, Dominguez, KM, Cheng, LSC, Ipp, E, Cantor, RM, Krass, KL, Keulen, ETP, Aouizerat, BE, Lusis, AJ & Rotter, JI 2001, 'Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p', Hypertension, vol. 38, no. 4, pp. 773-778.
Allayee H, De Bruin TWA, Dominguez KM, Cheng LSC, Ipp E, Cantor RM et al. Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. Hypertension. 2001;38(4):773-778.
Allayee, Hooman ; De Bruin, Tjerk W A ; Dominguez, K. Michelle ; Cheng, Li S C ; Ipp, Eli ; Cantor, Rita M. ; Krass, Kelly L. ; Keulen, Eric T P ; Aouizerat, Bradley E. ; Lusis, Aldons J. ; Rotter, Jerome I. / Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. In: Hypertension. 2001 ; Vol. 38, No. 4. pp. 773-778.
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abstract = "Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, α-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic α-adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.",
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AU - Cheng, Li S C

AU - Ipp, Eli

AU - Cantor, Rita M.

AU - Krass, Kelly L.

AU - Keulen, Eric T P

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AU - Rotter, Jerome I.

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