TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84876123086&partnerID=8YFLogxK
U2 - 10.3389/fgene.2012.00086
DO - 10.3389/fgene.2012.00086
M3 - Article
AN - SCOPUS:84876123086
SN - 1664-8021
VL - 3
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - JUN
M1 - Article 86
ER -