Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos

V. Saroja Voruganti, Paul B. Higgins, Sven O E Ebbesson, John Kennish, Harald H H Göring, Karin Haack, Sandra Laston, Eugene Drigalenko, Charlotte R. Wenger, William S. Harris, Richard R. Fabsitz, Richard B. Devereux, Jean W. MacCluer, Joanne E. Curran, Melanie A. Carless, Matthew P. Johnson, Eric K. Moses, John Blangero, Jason G. Umans, Barbara V. Howard & 2 others Shelley A. Cole, Anthony Gean Comuzzie

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1 A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10-28 and 10-5). A Bayesian quantitative trait nucleotide analysis showed thatrs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 1075 and 17) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.

Original languageEnglish (US)
Article numberArticle 86
JournalFrontiers in Genetics
Volume3
Issue numberJUN
StatePublished - 2012
Externally publishedYes

Fingerprint

Fatty Acid Desaturases
Inuits
Carnitine
Transferases
Erythrocytes
Liver
Single Nucleotide Polymorphism
Linoleoyl-CoA Desaturase
Genes
Unsaturated Fatty Acids
delta-5 fatty acid desaturase
Coronary Artery Disease
Fatty Acids
Nucleotides
Chromosomes
Genotype
Confidence Intervals
Enzymes

Keywords

  • Bayesian quantitative trait nucleotide analysis
  • Essential fatty acids
  • Single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Voruganti, V. S., Higgins, P. B., Ebbesson, S. O. E., Kennish, J., Göring, H. H. H., Haack, K., ... Comuzzie, A. G. (2012). Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos. Frontiers in Genetics, 3(JUN), [Article 86].

Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos. / Voruganti, V. Saroja; Higgins, Paul B.; Ebbesson, Sven O E; Kennish, John; Göring, Harald H H; Haack, Karin; Laston, Sandra; Drigalenko, Eugene; Wenger, Charlotte R.; Harris, William S.; Fabsitz, Richard R.; Devereux, Richard B.; MacCluer, Jean W.; Curran, Joanne E.; Carless, Melanie A.; Johnson, Matthew P.; Moses, Eric K.; Blangero, John; Umans, Jason G.; Howard, Barbara V.; Cole, Shelley A.; Comuzzie, Anthony Gean.

In: Frontiers in Genetics, Vol. 3, No. JUN, Article 86, 2012.

Research output: Contribution to journalArticle

Voruganti, VS, Higgins, PB, Ebbesson, SOE, Kennish, J, Göring, HHH, Haack, K, Laston, S, Drigalenko, E, Wenger, CR, Harris, WS, Fabsitz, RR, Devereux, RB, MacCluer, JW, Curran, JE, Carless, MA, Johnson, MP, Moses, EK, Blangero, J, Umans, JG, Howard, BV, Cole, SA & Comuzzie, AG 2012, 'Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos', Frontiers in Genetics, vol. 3, no. JUN, Article 86.
Voruganti, V. Saroja ; Higgins, Paul B. ; Ebbesson, Sven O E ; Kennish, John ; Göring, Harald H H ; Haack, Karin ; Laston, Sandra ; Drigalenko, Eugene ; Wenger, Charlotte R. ; Harris, William S. ; Fabsitz, Richard R. ; Devereux, Richard B. ; MacCluer, Jean W. ; Curran, Joanne E. ; Carless, Melanie A. ; Johnson, Matthew P. ; Moses, Eric K. ; Blangero, John ; Umans, Jason G. ; Howard, Barbara V. ; Cole, Shelley A. ; Comuzzie, Anthony Gean. / Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos. In: Frontiers in Genetics. 2012 ; Vol. 3, No. JUN.
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abstract = "The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1 A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10-28 and 10-5). A Bayesian quantitative trait nucleotide analysis showed thatrs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 1075 and 17) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.",
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T1 - Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases in Alaskan Eskimos

AU - Voruganti, V. Saroja

AU - Higgins, Paul B.

AU - Ebbesson, Sven O E

AU - Kennish, John

AU - Göring, Harald H H

AU - Haack, Karin

AU - Laston, Sandra

AU - Drigalenko, Eugene

AU - Wenger, Charlotte R.

AU - Harris, William S.

AU - Fabsitz, Richard R.

AU - Devereux, Richard B.

AU - MacCluer, Jean W.

AU - Curran, Joanne E.

AU - Carless, Melanie A.

AU - Johnson, Matthew P.

AU - Moses, Eric K.

AU - Blangero, John

AU - Umans, Jason G.

AU - Howard, Barbara V.

AU - Cole, Shelley A.

AU - Comuzzie, Anthony Gean

PY - 2012

Y1 - 2012

N2 - The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1 A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10-28 and 10-5). A Bayesian quantitative trait nucleotide analysis showed thatrs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 1075 and 17) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.

AB - The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1 A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10-28 and 10-5). A Bayesian quantitative trait nucleotide analysis showed thatrs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 1075 and 17) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.

KW - Bayesian quantitative trait nucleotide analysis

KW - Essential fatty acids

KW - Single-nucleotide polymorphisms

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