Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema.

Jonathan Covault, Helen Pettinati, Darlene Moak, Timothy Mueller, Henry R Kranzler

Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut 06030-2103, USA. covault@psychiatry.uchc.edu

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2004 May 15

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Hypotheses about relationships between changes in membrane lipids and mental illness have focused primarily on three long-chain polyunsaturated fatty acids: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Membrane deficiencies of these fatty acids have been reported in schizophrenia (AA, EPA, and DHA) and in depression (EPA and DHA). Long-chain fatty acid-CoA ligase type 4 (FACL4; MIM 300157) is a key enzyme involved in the metabolism of AA, EPA, and DHA. FACL4 selectively esterifies these fatty acids with co-enzyme A, forming acyl-co-A, which can then be incorporated into membrane phospholipid. We used niacin-induced dermal erythema as one index of AA metabolism to identify a common C to T single nucleotide polymorphism (SNP) in the first intron of the FACL4 gene (Xq22.3), which is associated with enhanced dermal erythema in both schizophrenia and control subjects. Male subjects with the T0 genotype showed greater dermal erythema following topical application of methylnicotinate, suggesting that this polymorphism may be in linkage disequilibrium with a functional polymorphism of the FACL4 gene that modulates re-sequestration of agonist-released free AA. We also examined the allele frequency of this polymorphism in 555 European-Americans (EA), including 229 control subjects, 198 subjects with major depression, 58 with schizophrenia or schizoaffective disorder, and 70 with alcohol dependence without co-morbid psychiatric illness. We observed a significant excess of the T allele in subjects with major depression, as compared with controls (49% vs. 38%; P = 0.003) and a non-significant excess of the T allele in schizophrenia (44%; P = 0.29). The allele frequency for subjects with alcohol dependence did not differ from controls. Copyright 2004 Wiley-Liss, Inc.

Citation

Jonathan Covault, Helen Pettinati, Darlene Moak, Timothy Mueller, Henry R Kranzler. Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2004 May 15;127B(1):42-7