Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression.
The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54 Males/59 Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P < 0.05) and lower content of arachidonic acid in plasma phosphatidylcholine (PC) (P = 0.052), lower index of Delta5 desaturation (P < 0.01) and unsaturation index (UI) (P < 0.001). In contrast, DD patients had higher concentrations of plasma glucose, insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.
Charles University in Prague, First Faculty of Medicine, 4th Department of Internal Medicine, General Teaching Hospital in Prague, Prague, Czech Republic. mirozem@centrum.cz
Miroslav
M
Zeman
Marek
M
Vecka
Marie
M
Jáchymová
Roman
R
Jirák
Eva
E
Tvrzická
Barbora
B
Stanková
Ales
A
Zák
D015126:8,11,14-Eicosatrienoic Acid / Q000097:blood; D016718:Arachidonic Acid / Q000097:blood; D001786:Blood Glucose; D002849:Chromatography, Gas; D003066:Coenzyme A Ligases / Q000235:genetics*; D003863:Depression / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000097:blood; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011863:Radioimmunoassay; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D010713:Phosphatidylcholines; D016718:Arachidonic Acid; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D015126:8,11,14-Eicosatrienoic Acid