Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia

Rebecca Mar-Heyming, Makoto Miyazaki, Daphna Weissglas-Volkov, Nicholas A. Kolaitis, Narimaan Sadaat, Christopher Plaisier, Päivi Pajukanta, Rita M. Cantor, Tjerk W.A. De Bruin, James M. Ntainbi, Aidons J. Lusis

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.

Original languageEnglish (US)
Pages (from-to)1193-1199
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Familial Combined Hyperlipidemia
Stearoyl-CoA Desaturase
Hepatocyte Nuclear Factor 4
Fatty Acids
Monounsaturated Fatty Acids
PPAR gamma
Pedigree
Dyslipidemias
Haplotypes
Genes
Triglycerides
Chromosomes
Enzymes

Keywords

  • Familial combined hyperlipidemia
  • Genetics
  • Hepatocyte nuclear factor 4 alpha
  • Peroxisome proliferator-activated receptor gamma
  • Stearoyl-coa desaturase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mar-Heyming, R., Miyazaki, M., Weissglas-Volkov, D., Kolaitis, N. A., Sadaat, N., Plaisier, C., ... Lusis, A. J. (2008). Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(6), 1193-1199. https://doi.org/10.1161/ATVBAHA.107.160150

Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. / Mar-Heyming, Rebecca; Miyazaki, Makoto; Weissglas-Volkov, Daphna; Kolaitis, Nicholas A.; Sadaat, Narimaan; Plaisier, Christopher; Pajukanta, Päivi; Cantor, Rita M.; De Bruin, Tjerk W.A.; Ntainbi, James M.; Lusis, Aidons J.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 28, No. 6, 01.06.2008, p. 1193-1199.

Research output: Contribution to journalArticle

Mar-Heyming, R, Miyazaki, M, Weissglas-Volkov, D, Kolaitis, NA, Sadaat, N, Plaisier, C, Pajukanta, P, Cantor, RM, De Bruin, TWA, Ntainbi, JM & Lusis, AJ 2008, 'Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 6, pp. 1193-1199. https://doi.org/10.1161/ATVBAHA.107.160150
Mar-Heyming, Rebecca ; Miyazaki, Makoto ; Weissglas-Volkov, Daphna ; Kolaitis, Nicholas A. ; Sadaat, Narimaan ; Plaisier, Christopher ; Pajukanta, Päivi ; Cantor, Rita M. ; De Bruin, Tjerk W.A. ; Ntainbi, James M. ; Lusis, Aidons J. / Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2008 ; Vol. 28, No. 6. pp. 1193-1199.
@article{8fa2fd1e676c40928ff2adfbbf1b78a6,
title = "Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia",
abstract = "Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.",
keywords = "Familial combined hyperlipidemia, Genetics, Hepatocyte nuclear factor 4 alpha, Peroxisome proliferator-activated receptor gamma, Stearoyl-coa desaturase",
author = "Rebecca Mar-Heyming and Makoto Miyazaki and Daphna Weissglas-Volkov and Kolaitis, {Nicholas A.} and Narimaan Sadaat and Christopher Plaisier and P{\"a}ivi Pajukanta and Cantor, {Rita M.} and {De Bruin}, {Tjerk W.A.} and Ntainbi, {James M.} and Lusis, {Aidons J.}",
year = "2008",
month = "6",
day = "1",
doi = "10.1161/ATVBAHA.107.160150",
language = "English (US)",
volume = "28",
pages = "1193--1199",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia

AU - Mar-Heyming, Rebecca

AU - Miyazaki, Makoto

AU - Weissglas-Volkov, Daphna

AU - Kolaitis, Nicholas A.

AU - Sadaat, Narimaan

AU - Plaisier, Christopher

AU - Pajukanta, Päivi

AU - Cantor, Rita M.

AU - De Bruin, Tjerk W.A.

AU - Ntainbi, James M.

AU - Lusis, Aidons J.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.

AB - Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.

KW - Familial combined hyperlipidemia

KW - Genetics

KW - Hepatocyte nuclear factor 4 alpha

KW - Peroxisome proliferator-activated receptor gamma

KW - Stearoyl-coa desaturase

UR - http://www.scopus.com/inward/record.url?scp=44849099288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44849099288&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.107.160150

DO - 10.1161/ATVBAHA.107.160150

M3 - Article

C2 - 18340007

AN - SCOPUS:44849099288

VL - 28

SP - 1193

EP - 1199

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 6

ER -