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The ELOVL fatty acid elongase 6 (ELOVL6), the only elongase related to de novo lipogenesis, catalyzes the rate-limiting step in the elongation cycle by controlling the fatty acid balance in mammals. It is located on pig chromosome 8 (SSC8) in a region where a QTL affecting palmitic, and palmitoleic acid composition was previously detected, using an Iberian x Landrace intercross. The main goal of this work was to fine-map the QTL and to evaluate the ELOVL6 gene as a positional candidate gene affecting the percentages of palmitic and palmitoleic fatty acids in pigs.
Methodology and Principal Findings
The combination of a haplotype-based approach and single-marker analysis allowed us to identify the main, associated interval for the QTL, in which the ELOVL6 gene was identified and selected as a positional candidate gene. A polymorphism in the promoter region of ELOVL6, ELOVL6:c.-533C>T, was highly associated with the percentage of palmitic and palmitoleic acids in muscle and backfat. Significant differences in ELOVL6 gene expression were observed in backfat when animals were classified by the ELOVL6:c.-533C>T genotype. Accordingly, animals carrying the allele associated with a decrease in ELOVL6 gene expression presented an increase in C16:0 and C16:1(n-7) fatty acid content and a decrease of elongation activity ratios in muscle and backfat. Furthermore, a SNP genome-wide association study with ELOVL6 relative expression levels in backfat showed the strongest effect on the SSC8 region in which the ELOVL6 gene is located. Finally, different potential genomic regions associated with ELOVL6 gene expression were also identified by GWAS in liver and muscle, suggesting a differential tissue regulation of the ELOVL6 gene.
Conclusions and Significance
Our results suggest ELOVL6 as a potential causal gene for the QTL analyzed and, subsequently, for controlling the overall balance of fatty acid composition in pigs.
Polymorphism in the ELOVL6 Gene Is Associated with a Major QTL Effect on Fatty Acid Composition in Pigs
Jordi Corominas, 1 , * Yuliaxis Ramayo-Caldas, 1 Anna Puig-Oliveras, 1 Dafne Perez-Montarelo, 2 Jose L. Noguera, 3 Josep M. Folch, 1 , 4 and Maria Ballester 1
Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality.
Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter.
Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 2.5 μm (PM2.5) and ≤ 10 μm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis.
The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced.
Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
Beelen R, Hoek G, Raaschou-Nielsen O, Stafoggia M, Andersen ZJ, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Fischer PH, Nieuwenhuijsen MJ, Xun WW, Katsouyanni K, Dimakopoulou K, Marcon A, Vartiainen E, Lanki T, Yli-Tuomi T, Oftedal B, Schwarze PE, Nafstad P, De Faire U, Pedersen NL, ostenson C-G, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Overvad K, Sørensen M, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita HB, Sugiri D, Kramer U, Heinrich J, de Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Jaensch A, Ineichen A, Tsai MY, Schaffner E, Probst-Hensch NM, Schindler C, Ragettli MS, Vilier A, Clavel-Chapelon F, Declercq C, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Vineis P, Brunekreef B. 2015. Natural-cause mortality and long-term exposure to particle components: an analysis of 19 European cohorts within the Multi-Center ESCAPE Project. Environ Health Perspect 123:525-533; http://dx.doi.org/10.1289/ehp.1408095
Natural-Cause Mortality and Long-Term Exposure to Particle Components: An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
Rob Beelen,corresponding author1 Gerard Hoek,1 Ole Raaschou-Nielsen,2 Massimo Stafoggia,3 Zorana Jovanovic Andersen,2,4 Gudrun Weinmayr,5,6 Barbara Hoffmann,6,7 Kathrin Wolf,8 Evangelia Samoli,9 Paul H. Fischer,10 Mark J. Nieuwenhuijsen,11,12 Wei W. Xun,13,14 Klea Katsouyanni,9 Konstantina Dimakopoulou,9 Alessandro Marcon,15 Erkki Vartiainen,16 Timo Lanki,17 Tarja Yli-Tuomi,17 Bente Oftedal,18 Per E. Schwarze,18 Per Nafstad,18,19 Ulf De Faire,20 Nancy L. Pedersen,21 Claes-Goran ostenson,22 Laura Fratiglioni,23 Johanna Penell,20 Michal Korek,20 Goran Pershagen,20 Kirsten Thorup Eriksen,2 Kim Overvad,24,25 Mette Sørensen,2 Marloes Eeftens,1 Petra H. Peeters,26,27 Kees Meliefste,1 Meng Wang,1 H. Bas Bueno-de-Mesquita,10, 27, 28 Dorothea Sugiri,6,7 Ursula Kramer,6,7 Joachim Heinrich,29 Kees de Hoogh,13 Timothy Key,30 Annette Peters,8 Regina Hampel,8 Hans Concin,31 Gabriele Nagel,5,31 Andrea Jaensch,5 Alex Ineichen,32,33 Ming-Yi Tsai,32,33,34 Emmanuel Schaffner,32,33 Nicole M. Probst-Hensch,32,33 Christian Schindler,32,33 Martina S. Ragettli,32,33 Alice Vilier,35,36,37 Francoise Clavel-Chapelon,35,36,37 Christophe Declercq,38 Fulvio Ricceri,39 Carlotta Sacerdote,40 Claudia Galassi,40 Enrica Migliore,40 Andrea Ranzi,41 Giulia Cesaroni,3 Chiara Badaloni,3 Francesco Forastiere,3 Michail Katsoulis,42 Antonia Trichopoulou,42 Menno Keuken,43 Aleksandra Jedynska,43 Ingeborg M. Kooter,43 Jaakko Kukkonen,44 Ranjeet S. Sokhi,45 Paolo Vineis,13 and Bert Brunekreef1,26
The effect of different leaving groups on the substitution versus elimination outcomes with C-5 d-glucose derivatives was investigated. The stereochemical configurations of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-d-glucofuranose, C36H38O8S (3) [systematic name: 1-[(3aR,5R,6S,6aR)-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-(trityloxy)ethyl methanesulfonate], a stable intermediate, and 5-azido-3-O-benzyl-5-deoxy-1,2-O-isopropylidene-6-O-triphenylmethyl-β-l-idofuranose, C35H35N3O5 (4) [systematic name: (3aR,5S,6S,6aR)-5-[1-azido-2-(trityloxy)ethyl]-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole], a substitution product, were examined and the inversion of configuration for the azido group on C-5 in 4 was confirmed. The absolute structures of the molecules in the crystals of both compounds were confirmed by resonant scattering. In the crystal of 3, neighbouring molecules are linked by C—H⋯O hydrogen bonds, forming chains along the b-axis direction. The chains are linked by C—H⋯π interactions, forming layers parallel to the ab plane. In the crystal of 4, molecules are also linked by C—H⋯O hydrogen bonds, forming this time helices along the a-axis direction. The helices are linked by a number of C—H⋯π interactions, forming a supramolecular framework.
crystal structure, iminosugar, d-glucofuranose, elimination, substitution, hydrogen bonding, C—H⋯π interactions
The crystal structures of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-d-glucofuranose and its azide displacement product
Zane Clarke,a,b Evan Barnes,a,c Kate L. Prichard,a,c Laura J. Mares,a Jack K. Clegg,d Adam McCluskey,a Todd A. Houston,e and Michela I. Simonea,c,*
2018 Jun 1