Fatty Acid CoA Ligase-4 Gene Polymorphism Influences Fatty Acid Metabolism in Metabolic Syndrome, but not in Depression

Fatty Acid CoA Ligase-4 Gene Polymorphism Influences Fatty Acid Metabolism in Metabolic Syndrome, but not in Depression

MIROSLAV ZEMAN,¹ MAREK VECKA,¹ MARIE JÁCHYMOVÁ,² ROMAN JIRÁK,³ EVA TVRZICKÁ,¹ BARBORA STANKOVÁ¹ and ALEŠ ZÁK¹

¹Charles University in Prague, First Faculty of Medicine, 4th Department of Internal Medicine, General Teaching Hospital in Prague, Prague, Czech Republic
²Institute of Clinical Biochemistry and Laboratory Diagnostics, Prague, Czech Republic
³Charles University in Prague, First Faculty of Medicine, Psychiatric Clinic, Prague, Czech Republic

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 (54Males/59Females), 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 Δ5 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.

keywords —— Long-chain fatty acid-CoA ligase 4; metabolic syndrome; depression; fatty acid; delta-5 fatty acid desaturase.

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Tohoku J. Exp. Med., 2009, 217, 287-293

Correspondence: Miroslav Zeman, MD, PhD, Charles University in Prague, 1st Faculty of Medicine, 4th Department of Internal Medicine, U Nemocnice 2, Prague 2-128 08, Czech Republic.

e-mail: mirozem@centrum.cz