FADS2 gene variant rs174593 is associated with multiple sclerosis

Abstract

Introduction: The hallmark pathogenic mechanisms of multiple sclerosis (MS) are proposed to be associated with long chain polyunsaturated fatty acids(LC-PUFA)-mediated neuroinflammation, through LC-PUFA-derived pro- and anti-inflammatory eicosanoids. Variants in genes coding for fatty acid desaturases (FADS), the key enzymes in LC-PUFA biosynthesis from essential fatty acids, are associated with changesin circulating LC-PUFA levels. The aim of thisstudy wasto investigate the FADS2 intronic variants, rs174576 (C/A), rs174593 (T/C) and rs174616 (G/A), in association with MS. Methods: The study involved 124 patients with relapsing-remitting form of MS and 83 healthy control subjects. The FADS2 gene variants were detected using TaqMan® SNP genotyping assays. Analysis of allele and genotype distributions in patients and controls was done by using the chi-square test. Results: According to the model of dominant effect of allele, genotypes containing the alternative, C, allele of FADS2 rs174593 variant were significantly less frequent in MS patients than in controls (MS: TT=57,26%, TC+CC=42,74%; controls: TT=42,17%, TC+CC=57,83%; p=0,03). In addition, the frequency of rs174593 C allele was significantly lower in patients, compared to controls (MS: T=0,76, C=0,24; controls: T=0,67, C=0,33; p=0,04). The frequency distributions of rs174576 and rs174616 alleles and genotypes were not significantly different between the study groups (p>0,05). Conclusion: The obtained resultssupply a rationale for further investigation of the association of FADS2 rs174593 with circulating LC-PUFA levels, in the context of MS. The genotype-LC-PUFA phenotype association could provide guidelinesfor personalized LC-PUFA supplementation, to potentially ameliorate the disease course and improve the effectiveness of therapy